Comparative study of spirapril (quadropril) and amlodipine efficacy. Results of randomized trial in patients with mild to moderate arterial hypertension

AIM: To compare in the non-blind randomised parallel study the efficiency of quadropril and amlodipine in the treatment of mild to moderate arterial hypertension. MATERIAL AND METHODS: A total of 80 patients (57.6 +/- 1.0 years) were included in this study. The patients were randomised in two groups, 40 patients each. Patients of group 1 received monotherapy with quadropril, while those of group 2 were treated with amlodipine. The treatment duration was 8 weeks in both groups. Quadropril was given in a fixed dose of 6 mg once daily. The initial dose of amlodipine was 5 mg/day. In case of insufficient effect the dose was elevated to 10 mg/day. The efficacy was evaluated by changes in blood pressure (BP) measured at rest. Moreover, in 50 randomly chosen patients 24-h monitoring of BP was performed at the start and end of the treatment. RESULTS: In the quadropril group baseline systolic BP reached 158.6 +/- 2.1 mm Hg, diastolic BP--101.8 +/- 0.8 mm Hg, heart rate was 74.3 +/- 1.6 beats/min. In the amlodipine group baseline systolic BP was 159.9 +/- 2.4 mm Hg, diastolic BP--101.8 +/- 1.0 mm Hg, heart rate was 71.3 +/- 1.0 beats/min. Systolic BP decreased at the end of quadropril therapy to 138.5 +/- 2.2 mm Hg, diastolic BP to 88.1 +/- 1.4 mm Hg. No significant change of the heart rate was observed. Under 5 mg of amlodipine systolic BP decreased to 137.9 +/- 2.5 mm Hg and diastolic BP to 87.1 +/- 1.6 mm Hg. Heart rate increased to 73.3 +/- 2.2 beats/min. Under therapy with 10 mg amlodipine systolic BP decreased to 145.9 +/- 3.8 mm Hg, diastolic BP to 89.7 +/- 3.4 mm Hg. Heart rate increased to 77.3 +/- 4.0 beats/min (p < 0.01). The hypotensive effect of quadropril remained stable while the effect of amlodipine decreased by the 8th week of therapy (p < 0.01). Side effects were observed significantly more often in the amlodipine group, then in the quadropril group. The main quadropril side effect was cough. Side effects observed in the amlodipine group were edemas, tachycardia, weakness. CONCLUSION: Both quadropril and amlodipine demonstrated a comparable antihypertensive effect although in 11 of 40 patients in the amlodipine group a dose increase was necessary and tolerability of quadropril was better.     

Efficacy of quadropril (spirapril) vs capropril in treatment of essential hypertension

AIM: To compare the efficacy of monotherapy with quadropril (spirapril) vs captopril in essential hypertension. MATERIAL AND METHODS: 20 female patients aged 55 +/- 2 years with moderate hypertension (WHO classification) were included in the study. 16 patients had congestive heart failure stage II NYHA and 4 patients stage III NYHA. ECG and echocardiography were performed in all the patients. Two patient groups of 10 patients were treated for 6 weeks. Group 1 received 6 mg quadropril once daily. Group 2 received 25 mg captopril 3 times daily. The therapy was considered to be efficient if diastolic pressure (BP) was reduced to 90 +/- 5 mm Hg and systolic BP to 140 +/- 10 mm Hg from baseline values in the range of 210/120-170/100 mm Hg. RESULTS: The hypotensive effect of quadropril resulted in stabilisation of BP during the second week of therapy. A significant BP decrease was achieved at the end of 6 week therapy. Systolic BP fell from 178.8 +/- 3.2 to 145 +/- 5.6 mm Hd and diastolic BP from 109.7 +/- 1.2 to 92.4 +/- 1.7 mm Hg. Central and cardiac hemodynamic parameters improved. In one patient the condition improved from CHF stage III to stage II NYHA. No adverse effects were observed. A hypotensive effect of captopril reduced significantly systolic blood pressure from 182.1 +/- 2.7 to 150 +/- 4.6 mm Hg and diastolic BP from 110.4 +/- 1.1 to 100.1 +/- 1.9 mm Hg. Two patients developed adverse effects: cough and chest dyscomfort. CONCLUSION: Quadropril monotherapy showed to be more effective in diastolic BP decrease compared with captopril monotherapy and had advantages in one daily dose regimen, absence of the first dose effect and side effects.     

Spirapril in patients with hypertension: clinical experience in Germany

AIM: To examine efficacy and tolerability of a single daily dose of 6 mg quadropril (spirapril). MATERIAL AND METHODS: An open multicenter study enrolled 5000 out-door patients with hypertension. All the patients received an ACE inhibitor quadropril for 3 months with four control visits (on week 0, 4, 8 and 12). RESULTS: Quadropril caused a marked decrease in systolic and diastolic blood pressure. At the end of the study 89.4% of patients had a systolic blood pressure reduction of at least 15 mm Hg and 85.4% had a diastolic blood pressure reduction of at least 10 mm Hg. There were no clinically significant heart rate changes. The overall tolerability of the drug was estimated as good or very good in 95.3% of patients. Only 2.9% of patients had side effects during treatment with once daily dose of 6 mg quadropril. No serious side effects were observed. CONCLUSION: 6 mg daily dose of quadropril is an effective and safe therapy for arterial hypertension.     

Use of alpha-adrenoblockers in therapy of benign prostatic hyperplasia in patients with arterial hypertension

AIM: To compare efficacy and tolerance of tonocardin (doxazosin) and omnik (tamsulosin) in the treatment of benign prostatic hyperplasia (BPH) in hypertensive patients. MATERIAL AND METHODS: Group 1 patients (n = 115, age 44-81 years) with BPH and mild or moderate arterial hypertension (AH) treated with one antihypertensive drug (ACE inhibitor--48, calcium antagonist--26, beta-blocker--22, diuretic--19) were given tonocardin in a single daily dose from 1 to 4 mg for 12 weeks. Group 2 patients (n = 30, age 67-81 years) with BPH and severe AH treated with two antihypertensive drugs and more were given omnik in a single daily dose 0.4 mg for 12 weeks. RESULTS: In group 1, tonocardin treatment resulted in lowering of a total symptoms score by IPSS scale from 17.5 +/- 3.6 to 14.7 +/- 1.3 points, of quality of life from 4.3 +/- 0.7 to 3.9 +/- 0.3, in a rise of maximal velocity of urine flow (Qmax) from 7.8 +/- 1.2 to 9.4 +/- 0.6 ml/s; residual urine (R) reduced from 112.4 +/- 8.6 to 64.5 +/- 10.2 ml). Systolic arterial pressure went down from 150.5 +/- 13 to 139.8 +/- 13.3 mm Hg, diastolic pressure fell from 86.9 +/- 6.1 to 80.8 +/- 7.1 mm Hg. In group 2, omnik resulted in IPSS scale points lowering from 17.7 +/- 3.5 to 15 +/- 1.1, QOL from 4.5 +/- 0.2 to 3.8 +/- 0.2, Qmax from 7.4 +/- 1.1 to 9.2 +/- 0.5 ml/s, R from 107.5 +/- 12.7 to 63.4 +/- 9.7 ml. Arterial pressure did not change much. CONCLUSION: Tonocardin and omnik are effective and safe not only in the treatment of BPH but also of BPH combination with AH.     

Angiotensin inhibition reduces glomerular damage and renal chemokine expression in MRL/lpr mice

Beneficial effects of angiotensin II inhibition during inflammatory renal disease may involve both hemodynamic and nonhemodynamic mechanisms. To analyze whether angiotensin II inhibition has protective effects on lupus-like, autoimmune-mediated renal damage in MRL/lpr mice, four groups of mice were treated orally for 6 weeks with: 1) vehicle, 2) enalapril (3.0 mg/kg per day), 3) candesartan cilexetil (5.0 mg/kg), or 4) amlodipine (10 mg/kg) as a blood pressure control (n = 9-12/group). All antihypertensive treatments lowered blood pressure to a similar level compared with vehicle group (enalapril: 99.8 +/- 8.3 mm Hg; candesartan: 101 +/- 9 mm Hg; amlodipine: 103.8 +/- 6.7 mm Hg; vehicle: 113.5 +/- 4.6 mm Hg). Vehicle-treated mice developed a moderate glomerular injury with albuminuria (35.1 +/- 39.0 microg/mg of creatinine). Glomerular lesions consisted of immune complex deposition and mesangial expansion with increased mesangial cell proliferation. Amlodipine treatment had no significant protective effects. In contrast to vehicle- and amlodipine-treated mice, those subjected to angiotensin II blockade with enalapril or candesartan had reduced albuminuria, glomerular expansion, and mesangial proliferation. This was associated with significantly reduced renal chemokine mRNA expression compared with vehicle treatment. Our results show that inhibition of angiotensin II has protective effects on the glomerular damage of MRL/lpr mice that extend beyond hemodynamics and involve down-modulation of glomerular inflammation, reduction of mesangial cell proliferation, and decrease in chemokine expression.     

Tonocardin in complex treatment of diabetes mellitus concurrent with hypertension

AIM: To examine the effect of the alpha 1-adrenoblocker tonocardin (doxazosin) on the course of arterial hypertension (AH) and on carbohydrate and lipid metabolism and insulin resistance in patients with type 2 diabetes mellitus (DM) concurrent with AH. MATERIALS AND METHODS: 18 patients with type 2 DM concurrent with AH, treated with tonocardin for at least 12 weeks were examined; the fasting glycemia, the levels of blood glycosylated hemoglobin, serum total cholesterol and triglycerides, and the degree of insulin resistance (intravenous insulin load or insulin tolerance test and the insulin resistance index estimated by the HOMA method) were determined. RESULTS: Tonocardin treatment lowered systolic BP (from 159 +/- 19.83 to 136.57 +/- 17.43 mm Hg; by 14.5%), diastolic BP (from 93.38 +/- 12.98 to 79.12 +/- 11.69 mm Hg; by 15.28%), fasting glycemia (from 9.32 +/- 1.61 to 7.05 +/- 1.51 mmole/l; by 24.36%), glycosylated hemoglobin Ai (from 9.63 +/- 1.86 to 8.59 +/- 0.98%; by 10.8%), total cholesterol (from 6.09 +/- 0.57 to 5.4 +/- 0.4 mmole/l; by 11.4%), triglycerides (from 2.11 +/- 0.57 to 1.88 +/- 0.52 mmole/l; by 11%), glycemia after 30-min insulin load (from 9.32 +/- 1.61 to 5.77 +/- 1.57; by 39% and from 7.05 +/- 1.51 to 4.2 +/- 1.25 mmole/l; by 44% at the beginning and end of the follow-up, respectively), insulin resistance index (from 9.87 +/- 2.45 to 6.57 +/- 1.99; by 33.5%). CONCLUSION: The findings suggest that tonocardin exerts an antihypertensive effect and positively affects carbohydrate and lipid metabolisms, and diminishes insulin resistance in patients with type 2 DM concurrent with AH.     

Comparison of rofecoxib,celecoxib, and naproxen on renal function in elderly subjects receiving a normal-salt diet

BACKGROUND: This study compared directly the renal effects of two selective cyclooxygenase (COX)-2 inhibitors (rofecoxib and celecoxib) with naproxen (dual COX-1/COX-2 inhibitor) and placebo in healthy elderly subjects on a sodium-replete diet. METHODS: A total of 67 elderly subjects stabilized in the clinic for weight and urinary sodium on a controlled 200-mEq sodium diet were randomized in a double-blind fashion to receive rofecoxib, 25 mg daily (n = 17); celecoxib, 200 mg twice daily (n = 17); naproxen, 500 mg twice daily (n = 17); or matching placebo (n = 16) for 28 days. Subjects were sequestered in the clinic for the first 14 treatment days on the controlled diet. RESULTS: Daily urinary sodium excretion during the first 72 hours of treatment (primary endpoint) significantly decreased in rofecoxib, celecoxib, and naproxen groups compared with baseline (P < or =.05). Rofecoxib and celecoxib decreases in urinary sodium excretion rates that were comparable with each other, on the basis of predefined boundaries (-39.5 versus -27.1 mEq/d, respectively) and to naproxen (-40.6, mEq/d). Rofecoxib, celecoxib, and naproxen increased mean systolic blood pressure to a similar degree (3.4, 4.3, and 3.1 mm Hg, respectively, versus -1.3 mm Hg for placebo) after 14 days of treatment; small changes also occurred in diastolic blood pressure (0.3, 0.8, and -0.4 mm Hg, respectively, versus -1.4 mm Hg for placebo). Changes from baseline in creatinine clearance, body weight, and urinary potassium excretion among active treatments were similar. After 28 days of treatment, findings were generally consistent with those at 14 days. No subject reported edema or discontinued treatment as the result of an adverse experience. CONCLUSION: In healthy elderly subjects on a sodium-replete diet, the COX-2 inhibitors rofecoxib and celecoxib did not differ from a nonselective nonsteroidal anti-inflammatory drug (naproxen), in influencing renal function as measured by urinary sodium excretion, systolic and diastolic blood pressure, creatinine clearance, or weight change.     

Experience in the use of valsartan with the aim to inhibit progression of kidney failure in patients with chronic glomerulonephritis

AIM: To assess the effect of valsartan, angiotensin-II receptor blocker type 1, on key factors of progression of chronic renal failure (CRF)--arterial hypertension (AH), proteinuria (PU), sodium excretion (SE)--in patients with chronic glomerulonephritis (CGN) and initial affection of renal function. MATERIAL AND METHODS: 11 patients (mean age 33.7 +/- 13.3 years, mean duration of nephritis 8.6 +/- 6.4 years, male to female ratio 8:3) with AH (AP > 140/90 mm Hg) and marked PU (> 1 g/day) who had not received immunosuppressive drugs for at least 6 months before the trial were given valsartan. It was administered after the period of "washing out" at the initial dose 80 mg/day with further addition of diuretics or raising the dose twice (in hyperuricemia) to decrease AP under 140/90 mm Hg. The duration of the treatment was 3 months. RESULTS: After 3 months of valsartan therapy systolic arterial pressure fell from 162 +/- 18 to 138 +/- 20 mm Hg (p < 0.05), diastolic pressure from 100 +/- 8 to 92 +/- 15 mm Hg (single measurements). 24-h monitoring of AP showed a significant lowering of mean 24-h and night systolic and diastolic AP, day-time diastolic AP, 24-h time index of systolic and diastolic AP. Initial antiproteinuric effect was observed after 1 month of the treatment and after 3 months of therapy PU reduced significantly (from 5.7 +/- 6.0 g/day to 3.3 +/- 3.3 g/day). After 3 months sodium excretion significantly rose, while creatinine level and glomerular filtration rate did not. Potassium rose in one patient. CONCLUSION: In CGN with initial CRF valsartan in a dose 80-160 mg/day produces a pronounced antihypertensive and antiproteinuric actions, stimulates sodium excretion. No serious side effects were noted. It is necessary to continue studies on the ability of valsartan to inhibit progression of CRF.     

Right ventricular infarction: recognition and assessment of its hemodynamic significance by two-dimensional echocardiography

To evaluate the ability of two-dimensional echocardiographic indexes to determine the hemodynamic significance of the right ventricular infarction, 24 patients with electrocardiographic evidence of right ventricular infarction were studied. Hemodynamic significance was defined as a jugular venous pressure greater than 17 cm H2O or a right atrial pressure greater than 13 mm Hg. Patients with hemodynamically significant right ventricular infarctions (group I, n = 9) had a 56% incidence of hypotension (blood pressure less than 90 mm Hg) with a mean systolic blood pressure of 93 +/- 23 mm Hg, whereas patients with nonhemodynamically significant right ventricular infarctions (group II, n = 15) had no hypotension and a mean systolic blood pressure of 121 +/- 18 mm Hg (p less than 0.01). The ratio of right atrial to pulmonary capillary wedge pressure was 1.1 +/- 0.6 in group I and 0.6 +/- 0.2 in group II (p less than 0.05). Echocardiography demonstrated right ventricular free wall motion abnormalities in seven patients in group I and in 10 patients in group II. The descent of the right ventricular base was 0.7 +/- 0.2 cm in group I, 1.3 +/- 0.4 cm in group II, and 2.0 +/- 0.2 cm in a group of 20 normal control patients (p less than 0.001 for all comparisons). The respiratory caval index (percentage of collapse of the inferior vena cava with inspiration) was 22% +/- 11% in group I, 45% +/- 15% in group II, and 64% +/- 17% in the control subjects (p less than 0.05 for all comparisons).(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of tissue myocardial dopplerechocardiography in early detection of structural-functional changes in the myocardium of patients with mild and moderate arterial hypertension

AIM: To study structural and functional changes in left ventricular myocardium (LVM) of patients with mild and moderate arterial hypertension (AH) with application of tissue myocardial dopplerechocardiography (TMD), correlation between these changes and parameters of electrophysiological remodeling and circadian profile of blood pressure. MATERIAL AND METHODS: Forty-give hypertensive patients were divided into two groups: the study group 2A consisted of 28 patients with mild AH (144.2 +/- 5.8/89.4 +/- 6.6 mm Hg), group 2B - of 17 patients with moderate AH (160.5 +/- 9.1/101.3 +/- 10.2 mm Hg). The control group consisted of 10 normotensive subjects. All the patients were examined using standard echocardiography with assessment of transmitral blood flow, tissue doppler investigation, circadian monitoring of blood pressure, electro-, vector- and decartocardiography. RESULTS: No significant differences in standard doppler, electro- and vectorcardiographic parameters between the patients with mild and moderate hypertension were found. LVM mass index and LV wall relative thickness significantly increased both in 2A and 2B groups vs controls (p < 0.05). Most patients of group 2A and 50% patients of group 2B had no alterations in LV geometry. Lower blood pressure was associated with LV concentric remodeling, higher - with concentric and excentric hypertrophy. In the presence of LV remodeling hypertensive patients developed more pronounced disorders of diastolic function according to TMD compared to hypertensive patients with normal LV geometry (p < 0.05). TMD detected LV diastolic disorders in 82% patients of group 2A and in 94% - of group 2B, while transmitral doppler study detected diastolic dysfunction only in 14 and 29% patients, respectively. A significant difference by Em/Am was registered between patients with mild and moderate AH only in the area of the mitral ring at the side of LV posterior wall (p < 0.05). CONCLUSION: TMD is able to detect earleast structural-functional myocardial changes in hypertensive patients and to determine significant differences in LV diastolic disorders in patients with mild and moderate AH. No significant differences in LVM mass, standard doppler, electro- and vector-cardiographic parameters were found between AH patients' groups.     

24-Hour blood pressure profile in patients with mild and moderate arterial hypertension and sleep apnea/hypopnea

AIM: To evaluate 24-hour blood pressure (BP) profile in arterial hypertension (AH) patients (pts) with desaturation signs of sleep apnea/hypopnea syndrome (SAHS). MATERIAL AND METHODS: We investigated 61 pts (44 males and 17 females) aged between 23-70 (52 +/- 2) years with mild to moderate AH. BP monitoring was performed with multisensor system TM-2425 (A&D, Japan). We assessed the following parameters: mean 24-h, awake, sleep systolic (S), diastolic (D) and pulse (P) BPs, systolic and diastolic BP loads ("normalized area under the curve"--NAUC). A normal circadian rhythm of BP was defined when nocturnal fall of SBP was > 10% and < 20%. The morning rise of BP we assessed by speed of increase of mean BP from 4 a.m. to 12 a.m. The nocturnal monitoring of arterial oxygen saturation(SaO2) was performed with pulseoximeter "NONIN 8500M" (USA). The analysis of the results was performed with the original program ARM-SaO2". The presence of SAHS was confirmed when the number of 4% desaturations were greater than 15 per hour or in the presence of group episodes of 4% desaturation below 90%. In 19 pts we revealed desaturation signs of SAHS. The comparison group included pts without SAHS (n = 42). We compared the groups regarding 24-h BP profile parameters. RESULTS: SAHS group had the following parameters significantly higher: mean 24-h (151.7 +/- 4.5 vs 142.9 +/- 2.4 mm Hg, p < 0.07) and sleep SBPs (142.8 +/- 5.1 vs 132.7 +/- 2.6 mm Hg, p < 0.05); mean 24-h (65.2 +/- 2.6 vs 55.9 +/- 1.9 mm Hg, p < 0.008), daytime (65.6 +/- 2.7 vs 56.6 +/- 2.0 mm Hg, p < 0.01) and sleep PBPs (64.1 +/- 2.7 vs 53.1 +/- 1.9 mm Hg, p < 0.002); 24-h (20.1 +/- 3.8 vs 12.6 +/- 1.8 mm Hg, p < 0.05) and sleep NAUC of SBP (24.6 +/- 4.4 vs 15.3 +/- 2.2 mm Hg, p < 0.03). In the group with SAHS were significantly higher the frequency of abnormal circadian rhythm of SBP (84 vs 57%, p < 0.05) and the speed of morning rise of mean BP (23.3 +/- 5.9 vs 8.5 +/- 2.8 mm Hg/h, p < 0.01). CONCLUSION: Our results suggest that pts with desaturation signs of SAHS are characterized by unfavourable changes in 24-h BP profile parameters, first of all owning to sleep systolic and pulse blood pressures with alteration of circadian rhythm and high speed of morning rise of BP.     

The role of hypersympathycotony in development of arterial hypertension in patients with metabolic syndrome: potential of pathogenetically sound therapy

AIM: To assess hypotensive efficacy and metabolic neutrality of moxonidine (physiotenz)--a selective agonist of imidasoline receptors--in patients with mild and moderate arterial hypertension (AH) associated with diabetes mellitus (DM) type 2. MATERIAL AND METHODS: Follow-up and treatment were conducted in 30 hypertensive diabetics (mean age 52.43 +/- 4.65 years). Mean duration of DM and AH was 4.77 +/- 2.69 and 6.93 +/- 2.98 years, respectively. The study was made of lipid exchange, glycemia, levels of glycosylated hemoglobin (GH), fasting and postprandial immunoreactive insulin. Hypotensive efficacy was examined by 24-h monitoring of arterial pressure after 16 weeks of therapy. RESULTS: Mean 24-h systolic arterial pressure fell by 8.02%, diastolic arterial pressure--by 6.47%. The drug had a good effect on a 24-h profile of arterial pressure: a significant decrease of day and night pressure load index, lowering of initially high 24-h variability of systolic and diastolic arterial pressure, normalization of two-phase profile of arterial pressure. Carbohydrate metabolism improved also: GH, glycemia, immunoreactive insulin decreased. There was a significant trend to a change in qualitative composition of blood lipid--a decrease in lipoproteins atherogenic fractions and a rise in HDLP. CONCLUSION: Physiotens is a highly effective hypotensive drug for use in mild and moderate AH in DM of type 2.     

Cerebral blood flow during the acute therapy of severe hypertension with oral clonidine

A major risk associated with the acute treatment of severe hypertension is a reduction in cerebral blood flow (CBF) with ischemic injury to the central nervous system. The authors studied CBF before and after the acute treatment of severe hypertension (diastolic blood pressure greater than 115 mm Hg) with clonidine in 13 patients. One patient did not reach goal blood pressure (diastolic blood pressure 105 mm Hg or a decrease by 30 mm Hg) after clonidine alone. In the remaining 12 patients, oral clonidine reduced supine blood pressure from 201.7 +/- 5.0/126.3 +/- 2.1 mm Hg to 149.4 +/- 5.3/96.8 +/- 1.7 mm Hg over an average time period of 85 +/- 7 minutes. Although mean CBF for the group did not change (72.6 +/- 4.2 v 73.7 +/- 3.5 mL/100 mg/min), a significant (greater than 10%) change occurred in 9 of the 12 patients (5 increases and 4 reductions). The magnitude and direction of the change were dependent upon initial CBF (r = -0.65, P less than .05); patients with low pretreatment CBF experienced an increase, whereas those with high initial flow exhibited a decrease. No significant adverse effects were observed. These data confirm previous reports that clonidine is effective in the acute treatment of severe hypertension and demonstrate that its effects on CBF are determined by the pretreatment levels of flow.     

A common beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to beta-blockade

BACKGROUND: A common polymorphism of the beta(1)-adrenergic receptor Arg389Gly markedly affects function in vitro, but little is known about its in vivo significance. METHODS AND RESULTS: Resting and exercise hemodynamic responses were measured in subjects homozygous for Arg389 (n = 21) or Gly389 (n = 13) alleles before and 3 hours after administration of a beta-blocker, atenolol. Demographic characteristics and atenolol concentrations were similar in the two genotypic groups. Genotype had a marked effect on resting hemodynamic responses to atenolol, with Arg389-homozygous subjects having a larger decrease in resting systolic blood pressure (8.7 +/- 1.3 mm Hg versus 0.2 +/- 1.7 mm Hg, P < .001) and mean arterial blood pressure (7.2 +/- 1.0 mm Hg versus 2.0 +/- 1.7 mm Hg, P = .009). Attenuation of exercise-induced hemodynamic responses by atenolol was not affected by genotype. CONCLUSIONS: There is reduced sensitivity of Gly389 homozygotes to a beta-adrenergic receptor antagonist, and this polymorphism may be an important determinant of variability in response to beta-blockade.     

Evaluation of isradipine (PN 200-110) in mild to moderate hypertension

The efficacy and safety of isradipine (PN 200-110), a new dihydropyridine calcium antagonist, was evaluated in 87 hypertensive patients in a placebo-controlled, double-blind, randomized multicenter trial. After a 3-week single-blind washout phase, isradipine (or matching placebo) was administered for 4 weeks, beginning at 2.5 mg b.i.d. with increments of 2.5 mg b.i.d. at weekly intervals if supine diastolic blood pressure remained greater than or equal to 90 mm Hg. At the end of 1 week average supine blood pressure in the isradipine group (n = 45) fell from a baseline of 156 +/- 13/104 +/- 4 mm Hg to 146 +/- 14/97 +/- 7 mm Hg. By week 4 blood pressure was reduced by 19/14 mm Hg compared with 4/5 mm Hg in the placebo group (P less than 0.001 between groups). Supine and standing pulse rates were slightly increased initially with isradipine therapy but returned to baseline with increasing isradipine doses. Blood pressure responses at week 4 were good or excellent (supine diastolic less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg decrease from baseline) in 87% of isradipine-treated patients and in 26% of placebo-treated patients. Headache, edema, abdominal discomfort, and constipation occurred slightly more frequently in isradipine-treated patients than in placebo-treated control subjects. The results indicate that isradipine, administered as monotherapy in doses of 2.5 to 10 mg b.i.d., is safe and effective in patients with mild to moderate essential hypertension.     

Depression in cardiological practice: pilot results from a multicenter clinico-epidemiological trial in hypertensive patients with ischemic heart disease (koordinata)

AIM: To study effects of depression on the course and prognosis of arterial hypertension (AH) and coronary heart disease (CHD), potentialities of the combined treatment in a prospective multicenter trial. MATERIAL AND METHODS: A total of 376 patients with AH and/or CHD having depression (10 scores and higher by HADS scale) were assigned to two groups: 189 (50.3%) patients received somatotropic therapy+coaxil (the study group), 187 (49.7%) patients received somatotropic therapy alone (the comparison group). Coaxil was given for 6 weeks in a dose of 37.5 mg/day, to patients over 70 years--25 mg/day. The effects were assessed by changes in HADS, CGI scale, blood pressure, heart rate; by tolerance and side effects (objective effects); complaints, well- being, stress, tolerance (subjective effects). RESULTS: The addition of coaxil to somatotropic therapy of patients with AH and/or CHD associated with depression led to improvement of the psychological status (a 36% decrease by HADS depression scale from 13.1 +/- 2.75 to 8.43 +/- 3.64, -delta4.76, p < 0.0001; by HADS anxiety scale--by 35.6% from 12.08 +/- 3.90 to 7.78 +/- 3.63, -delta4.31, p < 0.0001; by response to psychoemotional stress--by 23% from 6.65 +/- 1.94 to 4.77 +/- 1.85, -delta1.88, p < 0.05). Control patients also showed a positive trend in the above indices (a decrease in the above indices from 13.15 +/- 2.65 to 11.79 +/- 3.31, from 11.50 +/- 3.66 to 10.12 +/- 3.95, from 6.63 +/- 1.99 to 6.03 +/- 2.07, p < 0.05, respectively) but positive changes were much weaker than in the coaxil group (p < 0.001). To the end of the treatment, patients of the study group had less number of complaints, more patients achieved the target level of arterial pressure under 140/90 mm Hz (43.9 versus 29.9% in the control group; p < 0.005). CONCLUSION: Standard somatotropic treatment of AH patients with CHD and depression is not sufficiently effective. Combination of such treatment with antidepressive therapy (coaxil) significantly improves psychological status, and efficacy of therapy of basic cardiological diseases.     

Role of endogenous nitric oxide in circadian blood pressure regulation in healthy humans and in patients with hypertension or atherosclerosis.

BACKGROUND: Nitric oxide (NO) is involved in the regulation of blood pressure and local blood flow. Its biological activity is impaired in hypertension and atherosclerosis. Because blood pressure undergoes a circadian rhythm, we investigated whether systemic NO production is dependent on a circadian variability, and whether the phasing of diurnal rhythm in NO production corresponds to the one in blood pressure in humans. METHODS: We studied three groups of human subjects: 8 healthy volunteers (HV), 8 patients with essential hypertension (HT), and 8 patients with peripheral arterial occlusive disease (PAOD). Twenty-four-hour ambulatory blood pressure monitoring was performed simultaneously with eight consecutive 3-hour urine collection periods. Urinary nitrate excretion was measured by gas chromatography-mass spectrometry; urinary cyclic GMP excretion was assessed by RIA. RESULTS: Twenty-four-hour mean arterial blood pressure was 119.8 +/- 2.0/75.8 +/- 1.5 mm Hg in HV, 145.0 +/- 6.4/94.9 +/- 2.8 mm Hg in HT (P < 0.05 vs HV), and 137.0 +/- 7.3/81.5 +/- 1.9 mm Hg in PAOD (P = NS vs HV). There was significant circadian variation in blood pressure in all groups, but daily amplitude was lower in HT and PAOD than in HV (P < 0.05); 24-hour mean urinary nitrate excretion was 183.4 +/- 27.2 mumol/mmol creatinine in HV, 102.9 +/- 18.1 mumol/mmol creatinine in HT, and 162.1 +/- 22.2 mumol/mmol creatinine in PAOD (P < 0.05 vs HV and HT). Urinary cyclic GMP excretion was 211.8 +/- 19.0 nmol/mmol creatinine in HV, 108.6 +/- 12.4 nmol/mmol creatinine in HT, and 97.9 +/- 13.4 nmol/mmol creatinine in PAOD (P < 0.05 for HT and PAOD vs HV). Circadian variation was present in urinary nitrate and cyclic GMP excretion in HV but was significantly diminished in HT and PAOD, respectively; 24-hour mean nitrate-to-cyclic GMP ratio was 0.89 +/- 0.05 in HV and 1.10 +/- 0.10 in HT (P = NS). It was increased to 2.02 +/- 0.17 in PAOD (P < 0.05 vs HV and HT). CONCLUSIONS: There is significant circadian variation in urinary nitrate and cyclic GMP excretion rates, two marker molecules for systemic NO production, in healthy humans. NO production is increased in the morning, concomitantly with the morning increase in blood pressure, indicating that NO may buffer blood pressure increase. Diurnal variation in nitrate and cyclic GMP excretion is absent in HT, pointing to impaired NO formation. The major change in PAOD is increased nitrate/cyclic GMP ratio, which points to increased oxidative inactivation of NO in this disease. Disturbed formation and activity of NO may contribute to blood pressure alterations in cardiovascular disease.     

Cerebral response to norepinephrine compared with fluid resuscitation in ovine traumatic brain injury and systemic inflammation

OBJECTIVE: Traumatic brain injury is frequently accompanied by a systemic inflammatory response. Systemic inflammation was associated with cerebral hyperperfusion uncoupled to global oxygen metabolism in ovine head trauma. The present study investigated the cerebral effects of cerebral perfusion pressure (CPP) management performed by either fluid resuscitation or vasopressor treatment of low CPP induced by systemic inflammation. DESIGN: Nonrandomized experimental study. SETTING: University hospital laboratory. SUBJECTS: A total of 12 adult sheep. INTERVENTIONS, MEASUREMENTS, AND MAIN RESULTS: Sheep were anesthetized and ventilated throughout the experimental period (13 hrs). After baseline measurements (hour 0), blunt head trauma was induced by a nonpenetrating stunner. After postinjury measurements (hour 2), all animals received continuous endotoxin infusion. At hour 10, one group (n = 6) was infused with hydroxyethyl starch until CPP reached 60-70 mm Hg. A second group (n = 6) received norepinephrine for CPP elevation. In the norepinephrine group, blood was isovolemically exchanged by hydroxyethyl starch to achieve comparable hematocrit levels. Head trauma increased intracranial pressure and decreased brain tissue oxygen tension. Endotoxemia induced a hyperdynamic cardiovascular response with increased internal carotid blood flow in the presence of systemic hypotension and decreased CPP. Hydroxyethyl starch infusion further increased internal carotid blood flow from (mean +/- sd) 247 +/- 26 (hour 10) to 342 +/- 42 mL/min (hour 13) and intracranial pressure from 20 +/- 4 (hour 10) to a maximum of 25 +/- 3 mm Hg (hour 12) but did not significantly affect brain tissue oxygen tension, sinus venous oxygen saturation and oxygen extraction fraction. Norepinephrine increased internal carotid blood flow from 268 +/- 19 to 342 +/- 58 mL/min and intracranial pressure from 22 +/- 11 to 24 +/- 11 mm Hg (hour 10 vs. hour 13) but significantly increased sinus venous oxygen saturation from 49 +/- 4 (hour 10) to a maximum of 59 +/- 6 mm Hg (hour 12) and decreased oxygen extraction fraction. The increase in brain tissue oxygen tension during norepinephrine treatment was not significant. CONCLUSION: We conclude that despite identical carotid blood flows, only CPP management with norepinephrine reduced the cerebral oxygen deficit in this model.     

Blood pressure, plasma volume, and catecholamine levels during enalapril therapy in blacks with hypertension

The effect of enalapril, an antihypertensive inhibitor of angiotensin-converting enzyme, on plasma catecholamine levels and plasma volume (PV) has not been well established. In a randomized, double-blind study, 29 subjects (28 blacks and one white) received one of the following dosing regimens: hydrochlorothiazide (HCTZ), 25 mg twice a day (group 1; n = 12); enalapril, 10 mg twice a day (group 2; n = 12); or enalapril, 10 mg twice a day, with HCTZ, 25 mg twice a day (group 3; n = 5). Dosages were doubled after 4 wk if diastolic blood pressure was greater than or equal to 90 mm Hg. After 8 wk of therapy, supine blood pressure decreased by 24.1/16.0 mm Hg (systolic/diastolic) in group 1, by 10.8/4.0 mm Hg in group 2, and by 48.0/27.8 mm Hg in group 3. Mean values of supine plasma levels of norepinephrine, epinephrine, and dopamine did not change with therapy. PV fell 7.9% in group 1, 1.3% in group 2, and 5.0% in group 3. There were no correlations between changes in PV and blood pressure, but a decrease in PV correlated with an increase in plasma norepinephrine levels in the group treated with HCTZ alone (r = -0.65) and in all 29 subjects combined (r = -0.45). Enalapril alone was not very effective in lowering blood pressure in these subjects, but the combination of enalapril with HCTZ was very effective. There was no evidence of a direct effect of enalapril on the sympathetic nervous system or on PV.     

Effects of delapril in combination with indapamide on blood pressure and left ventricular mass in elderly hypertensive patients

We present a single-blinded, placebo-controlled trial of the effects on blood pressure and left ventricular mass and of the safety of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1) with sitting systolic/diastolic blood pressure of 160-200/95-115 mm Hg (at the end of the placebo period). After a 2-week placebo run-in, patients took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. Twenty-four-hour ambulatory blood pressure was monitored and M- and B-mode echocardiography were performed before and after 24 weeks of treatment. Blood pressure decreased from 156 +/- 1.5/101 +/- 1 mm Hg before treatment to 133 +/- 1/73 +/- 1 mm Hg after treatment. The total blood pressure burden also decreased; the percentage of measurements with a systolic blood pressure > or = 140 mm Hg and a diastolic blood pressure > or = 90 mm Hg decreased from 48.7% +/- 5%/31.5% +/- 4.3% to 23.5% +/- 4%/20.5% +/- 2.9% (p < 0.0005 and p < 0.05). The area under the curve of the 24-hour blood pressure decreased from 250 +/- 41/103 +/- 21 mm Hg to 97 +/- 21/37 +/- 8.5 mm Hg (p < 0.001 and p < 0.005). The left ventricular mass index (LVMI) in the 15 patients with pretreatment left ventricular hypertrophy was reduced after therapy from 167.5 +/- 8.5 g/m 2 to 152.2 +/- 7.6 g/m 2 (p < 0.05). A positive correlation was observed between percent changes of the area under the curve of the 24-hour diastolic blood pressure and percent changes of LVMI (r = 0.6; p < 0. 05) in the 15 patients with left ventricular hypertrophy. Only 2 patients reported side effects: 1 developed skin rash and 1 developed headache. The safety of the treatment was confirmed by laboratory tests. In elderly hypertensive patients, the combination of delapril and indapamide at low doses reduced blood pressure and had favorable effects on LVMI with few side effects.