Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. METHODS: We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. RESULTS: At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). CONCLUSIONS: Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.     

Elevated arterial blood pressure in cardiac tamponade.

BACKGROUND. In cardiac tamponade cardiac output falls, but peripheral vascular resistance increases, so that systemic blood pressure may be maintained at normal or near-normal levels. We recently observed a patient with cardiac tamponade whose blood pressure was markedly elevated. METHODS. To determine the frequency of elevated blood pressure in patients with cardiac tamponade and their hemodynamic characteristics, we studied 18 consecutive patients with cardiac tamponade from a variety of causes using right heart catheterization. RESULTS. Six of the 18 patients had systolic arterial blood pressures ranging from 150 to 210 mm Hg (mean [+/- SD], 176 +/- 26) and diastolic pressures ranging from 100 to 130 mm Hg (mean, 113 +/- 14). All six had previously been hypertensive. After pericardiocentesis there was a significant decrease in blood pressure (to 139 +/- 13 mm Hg systolic, P less than 0.05; and 83 +/- 6 mm Hg diastolic, P less than 0.01) and peripheral vascular resistance (from 2150 +/- 588 to 1207 +/- 345 dyn.sec.cm-5, P less than 0.01). Cardiac output increased in all six. The other 12 patients, 3 of whom had a history of hypertension, had significant increases in cardiac output and systolic blood pressure (from 119 +/- 13 to 127 +/- 7 mm Hg, P less than 0.05) after pericardiocentesis, whereas peripheral vascular resistance decreased. Both groups had similar degrees of cardiac tamponade, as indicated by measurements of cardiac output and intrapericardial, right atrial, and pulmonary-artery wedge pressures. CONCLUSIONS. Elevated blood pressure may occur in some patients with cardiac tamponade who have preexisting hypertension. Moreover, blood pressure may fall after pericardiocentesis in patients who have elevated blood pressure associated with tamponade.     

Sex-Specific Effects of AGT-6 and ACE I/D on Pulse Pressure After 6 Months on Antihypertensive Treatment: The GenHAT Study

Research suggests pulse pressure (PP) is a predictor of cardiovascular disease, and genes likely influence PP levels. Additionally, gender may be an effect modifier between PP and cardiovascular disease. This study addresses whether two renin-angiotensin-aldosterone system ( RAAS ) variants are associated with PP in a sex-specific manner (genotype-by-sex interaction).
Subjects comprised 35,048 GenHAT study participants over 55 years old, approximately half were women and half non-Hispanic white. Blood pressure measurements were obtained 6 months after randomization to one of four antihypertensive medications. The polymorphisms considered were AGT-6 and ACE -I/D. We employed linear regression to assess the interaction.
AGT-6 showed a significant (p < 0.001) genotype-by-sex interaction. Men with the 'G/G' genotype had a higher PP (0.6 mm HG) than men carrying an 'A' allele, while 'G/G' women had a lower PP (0.7 mm Hg) than women carrying an 'A' allele. Three of the four treatment groups (chlorthalidone, amlodipine and lisinopril) suggested a consistent interaction in sub-group analyses (only amlodipine was statistically significant, p < 0.001), whereas doxazosin did not. The interaction was evident among non-Hispanic participants but not among Hispanic participants. For ACE -I/D no evidence for a genotype-by-sex interaction was detected.
This finding of genotype-by-sex interaction on PP helps our understanding of the complexity of genetic effects on blood pressure.     

Suppressive effects of transdermal clonidine administration on contact hypersensitivity reactions in guinea pigs

In the present study, immunopharmacological effects of clonidine-TTS on allergic contact dermatitis (ACD) to non-related, established contact sensitizers were investigated in guinea pigs. First, to evaluate the hypotensive effect of clonidine-TTS in guinea pigs, intra-arterial blood pressure was recorded. After 4 days of treatment with one (or two) TTS per animal, a reduction of arterial blood pressure from 71 +/- 1 to 51 +/- 2 mm Hg was observed. We subsequently assessed the effects of clonidine-TTS on contact hypersensitivity reactions to 2,4-dinitrochlorobenzene (DNCB) and 4-ethoxymethylene-2-phenyl-oxazolone (Ox). This study indicates that clonidine-TTS suppressed the elicitation of contact hypersensitivity reactions. The observed immunosuppressive effect of clonidine may account for the relatively weak hypersensitivity reactions to this drug in experimental animal studies. Further studies are needed to determine whether such findings are of relevance to the clinical use of clonidine in patient populations.     

Online conductivity monitoring: validation and usefulness in a clinical trial of reduced dialysate conductivity

Relatively low dialysate conductivity (Cndi) may improve outcomes by reducing the overall sodium burden in dialysis patients. Excess sodium removal, however, could lead to hemodynamic instability. We performed a randomized controlled trial of reduction of Cndi. For the study, 28 patients were randomized to maintenance of Cndi at 13.6 mS/cm (equivalent to 135 mmol/L of Na+) or serial reduction of Cndi in steps of 0.2 mS/cm, guided by symptoms and blood pressure. Sodium removal estimated from pre- and postplasma concentrations correlated well with removal measured by conductivity monitoring as ionic mass balance (R2 0.66, p < 0.0001). Of the 16 patients randomized to reduction of Cndi, 6 achieved Cndi 13.4 mS/cm, 6 achieved 13.2 mS/cm, and 4 achieved 13.0 mS/cm. No episodes of disequilibrium occurred. Interdialytic weight gain was reduced from 2.34 +/- 0.10 kg to 1.57 +/- 0.11 kg (p < 0.0001). Predialysis systolic blood pressure fell from 144 +/- 3 mm Hg to 137 +/- 4 mm Hg (p < 0.05). The reduction in convective sodium removal was balanced by an increase in diffusive sodium removal (95 +/- 9 mmol cf. 175 +/- 14 mmol, p < 0.0001). Reduction in Cndi monitored by IMB is safe and practical and leads to improved interdialytic weight gains and blood pressure control, while avoiding excessive sodium removal.     

Hemodynamic and humoral effects of caffeine in autonomic failure. Therapeutic implications for postprandial hypotension

We examined the effects of caffeine and meals on blood pressure and heart rate in 12 patients with autonomic failure. The influence of caffeine on plasma norepinephrine, epinephrine, and renin activity was also studied. Caffeine 250 mg, raised blood pressure by 12/6 mm Hg, from 129 +/- 25/78 +/- 12 (mean +/- S.D.) to a maximum of 141 +/- 30/84 +/- 16 mm Hg at 45 minutes (P less than 0.01), but did not change heart rate, levels of norepinephrine, or epinephrine, or plasma renin activity. Blood pressure fell by 28/18 mm Hg after a standardized meal, from 133 +/- 32/80 +/- 15 to a minimum of 105 +/- 21/62 +/- 12 mm Hg at 60 minutes (P less than 0.01). After pretreatment with 250 mg of caffeine, the standardized meal induced a fall of only 11/10 mm Hg, from 140 +/- 33/79 +/- 7 to 129 +/- 31/69 +/- 13 mm Hg at 60 minutes (P less than 0.05 vs. values after the control per day for seven days) in five patients, postprandial blood pressures remained higher after caffeine than after placebo (P less than 0.05). We conclude that caffeine is a pressor agent and attenuates postprandial hypotension in autonomic failure, and that this effect is not primarily due to elevations in sympathoadrenal activity or activation of the renin-angiotensin system. Caffeine may be useful in the treatment of orthostatic hypotension due to autonomic failure, especially in the postprandial state.     

The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group

BACKGROUND: Patients with hypertension and renal-artery stenosis are often treated with percutaneous transluminal renal angioplasty. However, the long-term effects of this procedure on blood pressure are not well understood. METHODS: We randomly assigned 106 patients with hypertension who had atherosclerotic renal-artery stenosis (defined as a decrease in luminal diameter of 50 percent or more) and a serum creatinine concentration of 2.3 mg per deciliter (200 micromol per liter) or less to undergo percutaneous transluminal renal angioplasty or to receive drug therapy. To be included, patients also had to have a diastolic blood pressure of 95 mm Hg or higher despite treatment with two antihypertensive drugs or an increase of at least 0.2 mg per deciliter (20 micromol per liter) in the serum creatinine concentration during treatment with an angiotensin-converting-enzyme inhibitor. Blood pressure, doses of antihypertensive drugs, and renal function were assessed at 3 and 12 months, and patency of the renal artery was assessed at 12 months. RESULTS: At base line, the mean (+/-SD) systolic and diastolic blood pressures were 179+/-25 and 104+/-10 mm Hg, respectively, in the angioplasty group and 180+/-23 and 103+/-8 mm Hg, respectively, in the drug-therapy group. At three months, the blood pressures were similar in the two groups (169+/-28 and 99+/-12 mm Hg, respectively, in the 56 patients in the angioplasty group and 176+/-31 and 101+/-14 mm Hg, respectively, in the 50 patients in the drug-therapy group; P=0.25 for the comparison of systolic pressure and P=0.36 for the comparison of diastolic pressure between the two groups); at the time, patients in the angioplasty group were taking 2.1+/-1.3 defined daily doses of medication and those in the drug-therapy group were taking 3.2+/-1.5 daily doses (P<0.001). In the drug-therapy group, 22 patients underwent balloon angioplasty after three months because of persistent hypertension despite treatment with three or more drugs or because of a deterioration in renal function. According to intention-to-treat analysis, at 12 months, there were no significant differences between the angioplasty and drug-therapy groups in systolic and diastolic blood pressures, daily drug doses, or renal function. CONCLUSIONS: In the treatment of patients with hypertension and renal-artery stenosis, angioplasty has little advantage over antihypertensive-drug therapy.     

Cyclosporine-induced sympathetic activation and hypertension after heart transplantation

BACKGROUND. Hypertension is a frequent complication of cyclosporine-induced immunosuppression, but the underlying mechanism is unknown. In anesthetized animals, the administration of cyclosporine increases sympathetic-nerve discharge, which may contribute to hypertension. METHODS. To determine whether cyclosporine-induced hypertension is accompanied by sustained sympathetic neural activation in patients, we recorded sympathetic action potentials using intraneural microelectrodes (in the peroneal nerve) in heart-transplant recipients receiving azathioprine and prednisone alone (n = 5) or in combination with cyclosporine (n = 14). We performed the same studies in eight patients with myasthenia gravis who were receiving cyclosporine and eight who were not, in five patients with essential hypertension, and in nine normal controls. RESULTS. Heart-transplant recipients receiving cyclosporine had higher mean arterial blood pressure (+/- SE) than those not receiving cyclosporine (112 +/- 3 vs. 96 +/- 4 mm Hg; P less than 0.05) and a 2.7-fold higher rate of sympathetic-nerve firing (80 +/- 3 vs. 30 +/- 4 bursts per minute; P less than 0.05). For patients with myasthenia gravis, similar doses of cyclosporine were associated with smaller elevations in mean arterial blood pressure (100 +/- 2 mm Hg, as compared with 91 +/- 4 mm Hg in those not receiving cyclosporine; P less than 0.05) and in the rate of sympathetic-nerve firing (46 +/- 3 bursts per minute, as compared with 25 +/- 4 bursts per minute; P less than 0.05). Sympathetic activity in patients with heart transplants or myasthenia gravis who were not being treated with cyclosporine was no different from that in patients with essential hypertension or in normal controls. CONCLUSIONS. Cyclosporine-induced hypertension is associated with sympathetic neural activation, which may be accentuated by the cardiac denervation that results from heart transplantation.     

Antihypertensive efficacy and tolerability of once-daily sustained-release diltiazem alone and in combination with ramipril in hypertension

This study assessed once-daily (OD), sustained-release (SR) diltiazem alone and in combination with ramipril in essential hypertension. Fifty patients with supine diastolic blood pressure (DBP) > or = 95-< or = 114 mm Hg were entered into the active treatment phase of the study after 2 weeks of placebo run-in. Sustained-release diltiazem 180 mg OD was administered for 2 weeks, then optimally titrated, at 2 week intervals, to SR diltiazem 240 mg OD and then SR diltiazem 180 mg + ramipril 2.5 mg OD to achieve supine DBP < or = 90 mm Hg. After 4 weeks of diltiazem monotherapy (SR diltiazem 180 mg or 240 mg OD) mean supine DBP was reduced from 102.84 +/- 3.81 mm Hg to 90.15 +/- 5.02 mm Hg (P < 0.01) and mean supine heart rate was reduced from 85.15 +/- 11.02 bpm to 77.62 +/- 11.45 bpm (p < 0.01). Diltiazem monotherapy reduced supine DBP to < or = 90 mm Hg in 35/45 (77.77%) patients. Combination therapy (SR diltiazem 180 mg + ramipril 2.5 mg OD), received by non-responders to diltiazem monotherapy, reduced supine DBP to < or = 90 mm Hg in 3/10 (30%) patients. Sinus bradycardia was observed in one patient. Sustained-release diltiazem alone and in combination with ramipril reduce blood pressure in a dose related manner and is well tolerated.     

The pathogenesis of acute pulmonary edema associated with hypertension

BACKGROUND: Patients with acute pulmonary edema often have marked hypertension but, after reduction of the blood pressure, have a normal left ventricular ejection fraction (> or =0.50). However, the pulmonary edema may not have resulted from isolated diastolic dysfunction but, instead, may be due to transient systolic dysfunction, acute mitral regurgitation, or both. METHODS: We studied 38 patients (14 men and 24 women; mean [+/-SD] age, 67+/-13 years) with acute pulmonary edema and systolic blood pressure greater than 160 mm Hg. We evaluated the ejection fraction and regional function by two-dimensional Doppler echocardiography, both during the acute episode and one to three days after treatment. RESULTS: The mean systolic blood pressure was 200+/-26 mm Hg during the initial echocardiographic examination and was reduced to 139+/-17 mm Hg (P< 0.01) at the time of the follow-up examination. Despite the marked difference in blood pressure, the ejection fraction was similar during the acute episode (0.50+/-0.15) and after treatment (0.50+/-0.13). The left ventricular regional wall-motion index (the mean value for 16 segments) was also the same during the acute episode (1.6+/-0.6) and after treatment (1.6+/-0.6). No patient had severe mitral regurgitation during the acute episode. Eighteen patients had a normal ejection fraction (at least 0.50) after treatment. In 16 of these 18 patients, the ejection fraction was at least 0.50 during the acute episode. CONCLUSIONS: In patients with hypertensive pulmonary edema, a normal ejection fraction after treatment suggests that the edema was due to the exacerbation of diastolic dysfunction by hypertension--not to transient systolic dysfunction or mitral regurgitation.     

Ash Split Cath in geriatric dialyzed patients.

Vascular access is the essential step in performing hemodialysis in uremic patients. In the absence of a permanent and utilizable native arterio-venous fistula, the use of a tunnelled catheter makes dialysis therapy possible. The Ash Split Cath, a recently introduced chronic hemodialysis catheter, was inserted in five patients (7.1% of our prevalent dialysis population) because of repeated venous thrombosis in three patients and a poor venous tree in two. The mean age of patients was 78 years +/- 7. The average blood flow rate was 250+/-50 ml/minute and the mean venous pressure 140mm Hg +/- 35. Recirculation determined by low flux technique was less than 2%. KT/V calculated 3 months after the catheter placement was 1.2+/-0.02. During the follow-up we did not document any infection of the exit site or related to the catheter. This device is simple to place, gives adequate dialysis treatment and is useful in geriatric dialyzed patients in whom the arterio-venous fistula can no longer be used.     

Sleep apnea syndrome: a possible contributing factor to resistant

STUDY OBJECTIVES: There is evidence supporting an association between sleep apnea and hypertension. However, it is not clear if sleep apnea interteres with the pharmacotherapy of hypertension. To investigate this question, we studied the relationship between the effectiveness of anti-hypertensive treatment in reducing blood pressure, and severity of sleep apnea in a large group of apneic patients referred to a sleep disorders centre at St. Michael's Hospital at the University of Toronto. DESIGN: N/A SETTING: N/A PARTICIPANTS: 1,485 adult patients with sleep apnea, as defined by the apnea/hypopnea index (AHI) >10 events/hr, were analyzed. There were 393 who reported using anti-hypertensive medications on a regular basis for more than 6 months. One hundred and eighty-three patients were treated "effectively" (i.e. blood pressure lower than 140/90 mm Hg in the morning and in the evening). Seventy-four patients were treated "ineffectively," defined as blood pressure >140/90 mm Hg in the morning or in the evening. Both groups were compared with respect to clinical and demographic data using analysis of covariance with gender, age, body mass index (BMI), and neck circumference (NC) as covariates. INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Ineffectively and effectively treated patients were similar in age (57 +/- 9) vs. 57 +/- 10 years, respectively), and had similar body mass index (33.8 +/- 7.4 vs. 33.4 +/- 7.3 kg/m2, respectively). However, ineffectively treated patients had significantly higher apnea/hypopnea index (44 +/- 29 vs. 33 +/- 25 events/hr, p<.0005), despite having similar nocturnal oxygenation (percent of total sleep time spent with oxygen desaturation lower than 90% was 36 +/- 34 vs. 29 +/- 30% in the ineffective and effective groups, respectively). The difference in AHI persisted even after adjusting for age, gender, and body mass index. CONCLUSIONS: Our results demonstrate that hypertensive patients with sleep apnea whose blood pressure responds beneficially to treatment have less severe sleep apnea than those patients whose blood pressure remains elevated despite anti-hypertensive therapy. Since neither obesity nor nocturnal hypoxemia appear to be important determinants of ineffective treatment, we suggest that resistant hypertension may be caused by frequent intermittent sympathetic stimulation.     

Effect of intravenous infusion of verapamil in patients of severe hypertension

Thirty patients with diastolic blood pressure of 120 mm Hg or more were administered a bolus dose of verapamil (0.15 mg/kg) followed immediately by an intravenous infusion at a rate of 0.005 mg/kg/min for one hour. The patients were monitored during this period and three hours following the discontinuation of the infusion. The systolic, diastolic and mean blood pressures before verapamil administration were 221.4 +/- 7.5, 134.3 +/- 2.7 and 163.4 +/- 4.1 mm Hg respectively, which decreased to 170.1 +/- 5.2, 99.1 +/- 3.7 and 122.8 +/- 3.6 mm Hg after intravenous bolus of verapamil. The fall in all the levels of blood pressure was significant (p less than 0.001) and was maintained at the lower levels throughout the infusion period and even three hours after discontinuation of the therapy. No untowards effects were observed and there was no significant change in heart rate and electrocardiogram. It, thus, proves to be an useful addition to the therapeutic armamentarium in the acute management of severe hypertension.     

The effects of antihypertensive therapy on left ventricular mass in elderly patients

Left ventricular mass sometimes decreases during treatment of hypertension, but this response is inconsistent and its effects on left ventricular function are unknown. In a six-month randomized trial, we studied the ability of verapamil and atenolol to reduce left ventricular mass in 42 elderly patients with hypertension and the effects of this reduction in mass on cardiac function. The mean blood pressure (+/- SE) decreased in both the group that received verapamil (from 171.4 +/- 3.2/93.0 +/- 2.5 mm Hg to 142.9 +/- 2.8/79.0 +/- 2.0 mm Hg) and the group that received atenolol (from 179.6 +/- 4.6/98.5 +/- 2.4 mm Hg to 148.1 +/- 3.3/83.4 +/- 1.2 mm Hg), but the atenolol-treated patients more frequently required the addition of chlorthalidone to achieve blood-pressure reduction (P less than 0.01). Verapamil resulted in a reduction in the left-ventricular-mass index from 104 +/- 5 g per square meter of body-surface area to 85 +/- 5 g per square meter (P less than 0.01). Atenolol did not produce a reduction in the left-ventricular-mass index (109 +/- 9 g per square meter before treatment vs. 112 +/- 10 g per square meter after treatment). Two weeks after the withdrawal of antihypertensive therapy, blood pressure returned to pretreatment values. Nevertheless, in patients whose left ventricular mass had decreased, two measures of diastolic filling, the peak diastolic filling rate to the peak ejection rate, were significantly higher than before treatment (2.42 +/- 0.2 vs. 3.31 +/- 0.4 [P less than 0.05] and 0.61 +/- 0.03 to 0.85 +/- 0.05 [P less than 0.05], respectively). Diastolic filling was unchanged in the group that had no reduction in left ventricular mass. Cardiac output and the ejection fraction at rest and during mild exercise were unchanged in both groups as compared with baseline values. We conclude that left ventricular mass can be reduced in elderly patients with hypertension and mild ventricular hypertrophy who receive antihypertensive therapy. Reduction occurs more frequently with verapamil than with atenolol therapy, increases diastolic filling, and does not impair systolic function.     

Blood pressure reduced by methylene chloride. A study in spontaneously hypertensive rats

Effects of methylene chloride (CH2Cl2) on blood pressure (BP), body weight, plasma renin activity, hepatic histological structure of spontaneously hypertensive rats (SHRs) and normotensive control rats (NCRs) were studied. Administration of 0.15 mL/100 g/day CH2Cl2 to SHRs for five days reduced the BP from 172 +/- 7 mm Hg (mean +/- SEM) to 155 +/- 6 mm Hg without changing the plasma renin activity. The same regimen did not change the BP of NCRs. A weekly injection of 0.15 mL/100 g/day of CH2Cl2 for five consecutive weeks failed to significantly alter the BP of either SHRs or NCRs. The polyhalogen, whether administered daily or weekly, did not affect the body weight of either SHRs or NCRs. Administration of CH2Cl2 daily for five days produced an extensive but reversible hepatic centrolobular loss of glycogen in both SHRs and NCRs. No other changes were observed in the livers.     

Role of nitric oxide in haemodialysis hypotension

To investigate the possible involvement of nitric oxide (NO) in haemodialysis hypotension, we measured plasma concentrations of nitrate anion (NO3-), a metabolite of NO, in 114 patients undergoing maintenance haemodialysis. Mean plasma NO3- concentrations before dialysis were greater in subjects with lower blood pressure (155 +/- 16 micromol L-1) than in those with middle (117 +/- 8 micromol L-1) or higher blood pressure (105 +/- 12 micromol L-1) before dialysis. Further, mean plasma NO3- concentrations before dialysis were greater in subjects with lower blood pressure (186 +/- 13 micromol L-1) than in those with middle (112 +/- 7 micromol L-1) or higher blood pressure (64 +/- 11 micromol L-1) after dialysis. Plasma NO3- concentrations before dialysis were inversely correlated with mean blood pressure before dialysis (r=0.318, P=0.0006), and showed a strong inverse correlation with mean blood pressure after dialysis (r=0.608, P=0.0001). In the selected participants who had equal range of mean blood pressure before dialysis, mean plasma NO3- concentrations were greater in subjects with severe hypotension during dialysis (180 +/- 14 micromol L-1) than in those with mild hypotension (99 +/- 11 micromol L-1) or without hypotension (53 +/- 12 micromol L-1); plasma NO3- concentrations before dialysis were inversely correlated with changes in mean blood pressure during dialysis and mean blood pressure after dialysis. Results indicate that enhanced NO production may be involved in acute hypotension during dialysis, and suggest the possible involvement of NO in the pathogenesis of chronic hypotension associated with maintenance haemodialysis.     

Pulmonary vascular disease and hypertension after valve surgery for mitral stenosis

The reduction of pulmonary hypertension that occurs within 24 hours of valve replacement for mitral stenosis is well documented, but patients who die after surgery have not been adequately studied. Clinical and autopsy data for 16 patients who died following mitral valve replacement were reviewed. The emphasis was on preoperative and postoperative pulmonary arterial pressure and pulmonary vascular disease, including arterial, venous, and capillary changes. Morphologic features were graded and summed to obtain an additive histologic assessment (AHA). Patients were divided into three groups: 1) those who had uneventful operations and early postoperative periods but died prior to discharge; 2) those who had postoperative difficulty, with identifiable acute anatomic causes of death; and 3) those who had postoperative difficulty, with no apparent acute anatomic cause of death. In group 1 (n = 4) the preoperative pulmonary arterial pressure was 43 +/- 17 mm Hg, and AHA ranged from 0 to 4; in group 2 (n = 5) the preoperative pulmonary arterial pressure was 60 +/- 15 mm Hg, but AHA ranged only from 2 to 5. In group 3 (n = 7) the preoperative pulmonary arterial pressure was 59 +/- 12 mm Hg; AHA ranged from 6 to 9, significantly higher than that of the other groups (P less than 0.005). Three patients from group 3 had elevated pulmonary arterial pressure (60, 52, and 50 mm Hg three, six, and 15 days after surgery, respectively). Two additional patients had right heart failure with normally contracting left ventricles terminally. It is concluded that some patients with mitral stenosis who die after surgery with persistently elevated pulmonary arterial pressure have sufficiently severe pulmonary vascular disease to account for their persistent pulmonary hypertension and death.     

Response to exercise and ambulatory blood pressure monitoring in essential hypertension

To evaluate the relationship of ambulatory blood pressure (ABP) recording and blood pressure response to exercise, 58 essential hypertensive patients, not taking any drugs, had symptom-limited treadmill stress test (TST) within 48-96 hours of ABP, TST time, blood pressure increase, decrease, mode of increase and decrease, were independent of ABP systolic (SBP) and diastolic blood pressure (DBP) over 24 hours, day time and night time (p = ns). SBP decrease immediately after exercise were independent of ABP data. TST achieved heart rate was related to both 24 hours SBP (r = -0.64, p = 0.00005) and DBP (r = -0.55, p = 0.00001) in both day (r = -0.64, p = 0.00001 and r = -0.54, p = 0.002) and night (r = -0.52, p = 0.0001 and r = -0.46, p = 0.003) time periods. Therefore patients with achieved heart rate < 100% (n = 18) had higher 24 hour SBP (148 vs 132 +/- 2 mm Hg, p = 0.0006) and DBP (92.4 +/- 6.4 vs 84 +/- 6.2 mm Hg, P = 0.006) day and night. It is concluded that there is no overlap of diagnostic information using blood pressure. Values in TST or ABP although achieved heart rate in exercise is inversely related to severity of hypertension.     

An open clinical trial of benazepril--a new ACE inhibitor in mild-moderate hypertension

Benazepril hydrochloride, a new non-sulfhydryl ACE inhibitor (ACEI) was studied in a titrated dose of 10 mg-20 mg once a day for 6 weeks in 42 mild to moderate adult hypertensive patients with sitting diastolic blood pressure (SDBP) 95-114 mm Hg. The pre-drug SDBP(mean +/- SE) of 102.5 +/- 0.8 mm Hg showed a significant reduction to 87.5 +/- 0.93 mm Hg at the end of treatment. BP was controlled (SDBP < or = 90 mm Hg) in 34 (81%) patients and a drop of at least 10 mm Hg from the pre-treatment SDBP value was noted in 34 (81%) patients. Common adverse reaction was cough in 8(19%) patients. Clinically significant changes in laboratory evaluations were not seen in any patient. Study showed that benazepril in a dose range of 10 to 20 mg per day is an effective agent for treatment of mild to moderate hypertension.     

Acute and chronic stress influence blood pressure variability in mice

There is evidence that alterations in heart rate and blood pressure variability (BPV) are associated with cardiovascular disease. We used a mice model to investigate the effects of acute and chronic stress on blood pressure variability (BPV) and heat rate variability (HRV). Shaker stress was given acutely (5 min, 150 cycles/min) and chronically (3 days, 2 min stress, 150 cycles/min, 45 sessions/day) in male C57BLJ mice. Systolic arterial pressure (SAP) and pulse interval (PI) time series were submitted to autoregressive spectral analysis with variability measured in the low-frequency (LF, 0.1-1.0 Hz) and high-frequency (HF, 1-5 Hz) ranges. In the acute experiment, MAP was increased significantly in the first 10 min poststress period (99+/-2 vs. 113+/-2 mm Hg) and returned to control levels 30 min poststress. HR was significantly higher in the initial poststress period (537+/-12 vs. 615+/-20 bpm). These alterations were associated with a marked increase in BPV (21+/-4 vs. 55+/-11 mm Hg2) and in power of LF oscillations (18+/-3 vs. 42+/-7 mm Hg2). On the other hand, chronic stress exposure produced a reduction in BPV (16+/-4 vs. 6+/-1 mm Hg2) and LF oscillations (11+/-3 vs. 3+/-1 mm Hg2). HRV was not altered after either acute or chronic stress. Spontaneous baroreflex sensitivity (SBS), determined by cross-spectral analysis between PI and BP, was reduced significantly in acute stress (-50%), but unchanged in chronic stress. Our results show that acute stress produced changes in BPV that may be associated with increased sympathetic activity and a reduction in blood pressure buffering. Under chronic conditions, there is no alteration in baroreflex sensitivity while BPV is reduced. This is likely related to the combination of sympathetic activation in the face of vasculature alterations.