Acute and chronic effects of lisinopril on renal and systemic hemodynamics in hypertension

Summary Acute and chronic effects of the converting enzyme inhibitor lisinopril on renal and systemic hemodynamics were studied in 12 patients with mild to moderate essential hypertension. After a washout period, cardiac output (measured by Doppler echography), renal plasma flow, and glomerular filtration rate (measured by isotopic techniques) were determined before and after oral administration of 20 mg lisinopril (vist 1). The same protocol was repeated after 3 months of lisinopril therapy 20 mg once daily (visit 2). Acute administration of lisinopril, both in untreated hypertensive patients (visit 1) and during long-term treatment (visit 2), decreased blood pressure (p < 0.05) and increased renal plasma flow (p < 0.05), while cardiac output and glomerular filtration rate were unchanged. Comparison of baseline parameters between visits 1 and 2 showed that chronic treatment with lisinopril decreased blood pressure and renal vascular resistance and that these effects were still significant 24-hours postdosage. We conclude that lisinopril is an effective antihypertensive agent with favorable renal hemodynamic effects.     

Repetitive natriuresis and blood pressure. Long-term calcium entry blockade with isradipine

The long-term effects (3.5 months) of a new calcium entry blocker of the 1-4-dihydropyridine class, isradipine (PN 200-110), on renal hemodynamics and excretional parameters were investigated in 10 essential hypertensive subjects (World Health Organization Classes I and II). Blood pressure and renal vascular resistance fell significantly (p less than 0.001), and a slight increase in glomerular filtration rate and renal plasma flow was seen (p less than 0.05). Output of fluid from the proximal tubules, measured as clearance of lithium and uric acid, increased significantly (p less than 0.01 and p less than 0.05, respectively), and a compensatory increase in absolute reabsorption of sodium beyond the proximal tubular level accompanied by an increase in clearance of potassium was noted. A 40% increase in the resultant clearance of sodium (p less than 0.01) and an increase in diuresis (p less than 0.05) followed the morning dose of isradipine after 3.5 months of treatment. Changes in blood pressure were significantly correlated with changes in absolute proximal reabsorption of sodium (r = 0.81), excretion of sodium (r = -0.64), and diuresis (r = -0.80). Thus, the natriuretic properties of calcium entry blockers may be more important for the long-term antihypertensive effect than the vasodilator effect per se. A model for renal sodium handling following treatment with calcium entry blockers was proposed. Although a causal relationship is not implied, isradipine induced a sustained, repetitive postdose effect on proximal fluid output, net natriuresis, and diuresis, that was intimately related to the long-term blood pressure-regulating response.     

Cardiovascular effects of isradipine in essential hypertension

The immediate and short-term cardiovascular effects of oral isradipine therapy were evaluated in 11 patients with mild to moderate systemic hypertension. Isradipine, 5 mg administered orally, induced a significant reduction in arterial pressure from 165 +/- 6/88 +/- 3 mm Hg to 140 +/- 5/76 +/- 2 mm Hg (p less than 0.001) within 2.5 hours by a decrease in total peripheral resistance associated with an increase in heart rate and cardiac output. Contrary to the acute effect, oral therapy with isradipine for 3 months reduced arterial pressure through a decrease in total peripheral resistance but without causing an increase in heart rate or cardiac output or activation of the sympathetic nervous system. Isradipine slightly reduced left ventricular mass and improved cardiac systolic function and left ventricular filling. Renal blood flow increased, and renal vascular resistance (p less than 0.01) and total blood volume (p less than 0.002) decreased without a change in either sodium excretion or body weight. Thus, isradipine, when given for 3 months, decreased arterial pressure by reducing total peripheral resistance without activation of reflexive mechanisms. Its favorable effects on systemic hemodynamics, total blood volume, renal blood flow, and cardiac structure and function suggest isradipine to be an excellent choice for antihypertensive therapy.     

Calcium antagonists for initial therapy of hypertension

A new class of antihypertensive agents has emerged for clinical consideration in the initial treatment of hypertension. These calcium antagonists are rapidly absorbed and reduce arterial pressure very promptly by antagonizing the pathophysiologic hallmark of the disease: an increased vascular resistance. Moreover, in reducing arterial pressure by means of arteriolar dilation, these agents do so without expanding intravascular volume and without inordinately stimulating the heart through reflex mechanisms. Vascular resistance is reduced in each of the major target organs of the disease: the heart, brain, and kidney. Reduction of coronary vascular resistance should be of particular value in patients with increased myocardial oxygen demands (e.g., with coronary arterial disease or with ventricular hypertrophy). Reduction of renal vascular resistance should be especially valuable for patients with renal functional impairment as a result of hypertensive vascular disease or with associated renal parenchymal diseases. In this respect, these agents reduce renal vascular resistance while maintaining glomerular filtration rate and reducing renal filtration fraction; these changes should reduce glomerular hyperfiltration and may inhibit promotion of glomerulosclerosis. Diltiazem may be of particular value because it may produce these effects while increasing renal blood flow. Clearly these agents reverse cerebral constriction and might be expected to improve blood flow to the brain; however, further study is anticipated and necessary.     

Antihypertensive and hemodynamic effects of calcium channel blockade with isradipine after acute exercise.

In a randomized, double-blind, placebo-controlled, crossover study with two 4-week treatment periods, we investigated the effects of calcium channel blockade with 5 mg slow release oral isradipine on postexercise blood pressure and systemic hemodynamics (echocardiography) in ten hypertensive patients. The results show that the combination of exercise and isradipine treatment exerts additive antihypertensive effects in hypertensive patients after exercise. The antihypertensive effect of prior exercise with placebo was related to a significant fall in total peripheral resistance. After exercise during isradipine treatment, total peripheral resistance was lower than with placebo. Thus, isradipine exerts an additional antihypertensive effect during the postexercise period, which appears to be mediated by a further reduction of total peripheral resistance.     

Comparison of renal hemodynamics in early non-insulin-dependent and insulin-dependent diabetes mellitus

The differences in deranged renal hemodynamics in non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) have never been fully investigated. Whether or not autoregulatory mechanism of renal hemodynamics in NIDDM and IDDM is preserved remains to be clarified.In the present study we directly compared renal hemodynamics and its autoregulatory function in the early stage of NIDDM and IDDM before and after short-term glycemic control. Before glycemic control, mildly exaggerated glomerular filtration rate (GFR), subnormal renal plasma flow (RPF), and elevated filtration fraction (FF) were found in NIDDM as well as in IDDM; but there were no differences in these parameters of renal hemodynamics between the two types of diabetics. Glycemic control decreased GFR, whereas it did not alter RPF, resulting in normalization of FF in NIDDM and in IDDM. Before glycemic control, mean blood pressure was significantly correlated with GFR, but was not correlated after glycemic control in either type of diabetes. In conclusion, hyperglycemia induced glomerular hyperfiltration evenly and disturbed autoregulation of renal hemodynamics in NIDDM and in IDDM.     

Antihypertensive efficacy and effects of nitrendipine on cardiac and renal hemodynamics in mild to moderate hypertensive patients: Randomized controlled trial versus hydrochlorothiazide

Summary In this study antihypertensive efficacy, safety, and the effects of short-term nitrendipine administration on central and renal hemodynamics were evaluated in mild to moderate hypertensives. Our final goal was to ascertain whether the reduction in blood pressure induced by nitrendipine treatment was associated with maintained renal function. After a run-in period with placebo, 26 hypertensives without cardiac or renal disease were randomly assigned to a double-blind 8-week controlled trial with nitrendipine (N) 20 mg once a day (13 pts) or hydrochlorothiazide (HCT) 25 mg once a day (13 pts). Renal hemodynamic measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using I-131 hippuran and Tc-99m, according to the methods described by Schlegel and Gates, respectively. Effective renal blood flow [ERBF=ERPF/(1-Ht)], filtration fraction (FF=GFR/ERPF), and renal vascular resistance (RVR=MBP×80/ERBF) were also calculated. Other hemodynamic measurements included cardiac index (CI), left ventricular (LV) ejection fraction (EF), and total peripheral resistance (TPR) measured by the first-pass radionuclide angiography technique. At the end of N or HCT administration significant descreases (p<0.001) in SBP, DBP, and MBP vs. baseline values were observed in both hypertensive groups. In the N group a significant decrease (p<0.01) in TPR and RVR, and significant increases (p<0.05) in CI, ERPF, and ERBF were observed. In the HCT group a significant decrease (p<0.05) in RVR was found without significant changes in other hemodynamic parameters. No important side effects were observed with either therapy. In conclusion, nitrendipine was effective in reducing blood pressure in mild to moderate hypertensive patients and exerted favorable effects on cardiac and renal function.     

Renal effects of diltiazem in primary hypertension

Although the calcium channel blocker diltiazem has been shown to be an effective antihypertensive agent, its effect on renal function, salt and water excretion, and body fluid composition has not been well characterized in patients with primary hypertension. Therefore, these parameters were prospectively studied in 18 subjects with primary hypertension after placebo and 8 weeks of diltiazem monotherapy. Diltiazem monotherapy was confirmed to be an effective antihypertensive agent. Although mean arterial pressure was reduced from 121 to 108 mm Hg, diltiazem had no overall effect on glomerular filtration rate, renal plasma blood flow, salt and water excretion, or body fluid composition. Renal vascular resistance, however, was decreased. In subjects with pretreatment glomerular filtration rates of 80 ml/min/1.73 m2 or less, diltiazem therapy was associated with marked improvement in glomerular filtration rate (48%) and effective renal plasma flow (36%). Since the filtration fraction was unchanged, changes in glomerular filtration rate may have been related to the attenuated intrarenal effects of angiotensin II or norepinephrine, or both.     

Systemic and renal effects of a new angiotensin converting enzyme inhibitor, benazepril, in essential hypertension

Seventeen essential hypertensive patients with normal renal function were treated with a new non-sulphydryl orally active angiotensin converting enzyme (ACE) inhibitor, benazepril, 10 mg given once or twice daily, according to diastolic blood pressure levels, for 6 weeks. In all patients, changes in blood pressure, systemic and renal hemodynamics, plasma renin activity and urinary aldosterone and albumin excretions were assessed at the end of a 2-week placebo run-in period and at the end of the study. Benazepril monotherapy controlled blood pressure well. No changes in cardiac output, heart rate or stroke volume were observed, while peripheral vascular resistance was significantly decreased (-11%, P less than 0.05). Plasma volume was unaltered. The glomerular filtration rate was stable, but effective renal plasma flow was increased because of the marked reduction in renal vascular resistance (-35%) and, therefore, the filtration fraction was decreased. Urinary albumin excretion remained unchanged. A significant increase in plasma renin activity (P less than 0.001) and a decrease in urinary aldosterone excretion were seen. No side effects were observed during the treatment period. In conclusion, our results suggest that benazepril alone is an effective antihypertensive agent in patients with essential hypertension. The blood pressure lowering effect is due mainly to systemic vasodilation and is observed up to 24 h after administration of the drug. The vasodilation appears to be more consistent in the renal than in the systemic circulation.     

Effects of calcium antagonists on the hypertensive kidney

Summary This review focuses on the effects of calcium antagonists on renal function in hypertensive human subjects. Specifically assessed are the acute and chronic effects of diltiazem, verapamil, amlodipine, felodipine, isradipine, nicardipine, nifedipine, and nitrendipine on glomerular filtration rate; effective renal plasma flow/renal blood flow; renal vascular resistance; and urinary protein excretion. Among the calcium antagonists, only the dihydropyridine derivatives have been demonstrated consistently to acutely increase effective renal plasma flow/renal blood flow. The acute effects on glomerular filtration rate are variable. With respect to chronic therapy, many of the calcium antagonists have been reported to produce sustained increases in the effective renal plasma flow/renal blood flow and/or the glomerular filtration rate. Renal vascular resistance is reduced. Although calcium antagonists preserve or improve renal perfusion and glomerular filtration, long-term clinical trials are required to determine their potential therapeutic benefit to modify the natural course of hypertensive renal disease.     

Effects of enalapril and isradipine alone and in combination on blood pressure, renal function and echocardiographic parameters in mild hypertension

AIMS AND METHODS: A study was carried out to evaluate the influence of antihypertensive treatment with combined low doses of enalapril plus isradipine (5+5 mg daily) compared with those of either drug at a higher dose level (10 mg daily) by double-blind, three-way crossover study (balanced Latin square design) in 102 subjects (mean age 51.9 +/- 7.42 years) with essential hypertension. Left ventricular mass and function were evaluated by M-B mode echocardiography, renal function by glomerular filtration rate (GFR) and by serum and 24-h urinary Na+ and K+ during wash-out period and after 24 weeks of treatment. RESULTS: The supine blood pressure for subjects given placebo was 171/103 mmHg. After 24 weeks of treatment, systolic and diastolic supine blood pressure were significantly lower with 5 mg isradipine plus 5 mg enalapril (134/84 mmHg) than with 10 mg enalapril (137/84 mmHg) or with 10 mg isradipine (144/85 mmHg). Left ventricular posterior wall and septal thickness were significantly and similarly reduced in all groups. Left ventricular systolic and diastolic end diameters were not significantly changed. Left ventricular mass (LVM) was significantly reduced in E plus I group and enalapril group. GFR was not significantly altered. The 24-h urinary Na+ significantly increased with enalapril, more so than isradipine. The combination was tolerated better than either monotherapy. We observed no clinically significant changes in laboratory variables including blood lipoproteins. CONCLUSIONS: The combination of isradipine plus enalapril reduced blood pressure more effectively and was better tolerated than other drug alone. All three groups showed similar changes in echocardiographic indices and no change in renal function.     

Renal and hemodynamic effects of endothelin in anesthetized dogs

The effects of endothelin on systemic hemodynamics and renal functions were investigated in anesthetized dogs. Infusion of endothelin at a dose of 1 ng/kg/min decreased renal blood flow and increased renal vascular resistance and filtration fraction. Endothelin at doses higher than 10 ng/kg/min significantly decreased cardiac output, glomerular filtration rate, renal plasma flow, urine volume, and urinary sodium excretion. Mean arterial pressure showed a transient decrease at doses higher than 50 ng/kg/min. These results showed that endothelin in systemic administration has effects on renal functions as well as on systemic hemodynamics.     

Effect of long term therapy with captopril on dopplerographic parameters of intrarenal blood flow and renal function in patients with hypertension and diabetes

Effect of 9-12 month treatment with captopril on dopplerographic parameters of intrarenal blood flow and renal function was studied in 30 hypertensive diabetics without clinical signs of nephroangiopathy. There was an interrelationship between strict blood pressure (BP) control (average 24-hour BP below 135/83) and improvement of parameters of intrarenal hemodynamics. BP normalization and most pronounced positive changes of renal perfusion during therapy with captopril were achieved in patients with mild hypertension and initially high intrarenal resistance yet at the stage of normo- or microalbuminuria. In moderate hypertension with microalbuminuria treatment with captopril was associated with stabilization of parameters of renal blood flow and rate of 24-hour albumin excretion at their initial level despite less strict control of BP and unsatisfactory compensation of diabetes. BP response to captopril in patients with hypertension and diabetes was related to initial state of intrarenal hemodynamics. In patients with mild hypertension indexes of resistance of renal and intrarenal arteries could be used for prediction of sensitivity to antihypertensive action of captopril.     

Identification of normal neurohormonal activity in mild congestive heart failure and stimulating effect of upright posture and diuretics

To characterize further the pathophysiology of the neurohormonal vasoconstrictor pathways in congestive heart failure (CHF), plasma renin activity, plasma norepinephrine, blood pressure, blood volume and renal hemodynamics were measured in 12 patients with mild to moderate CHF. In addition, the response to the gravitational stress of head-up tilt and the influence of 3 weeks of furosemide treatment as stimuli of neurohormonal activity were assessed. Supine plasma renin activity before diuretics was relatively normal at 1.94 ± 1.6 ng/ml/hr and was significantly increased to 3.9 ± 2.7 ng/ml/hr after diuretics. During tilt, there was a significant reflex increase in plasma renin activity both before and after diuretics. Plasma norepinephrine was also relatively normal before diuretics (325 ± 211 pg/ml), did not increase after diuretics, but showed significant increases during tilt both before and after diuretics. Diuretic administration led to decreases in both systolic and diastolic blood pressures, but there was no change in body weight or total blood volume. In addition, diuretic administration did not result in any significant changes of renal blood flow (546 ± 119 to 634 ± 204 ml/min/ 1.73m²), glomerular filtration rate (81 ± 22 to 90 ± 27 ml/min/1.73m²) or filtration fraction (0.26 to 0.25). The present study demonstrates that the renin-angiotensin system and the sympathetic nervous system were not activated in the early symptomatic stages of CHF and that baroreceptor stimulation of these pathways during head-up tilt was relatively preserved. Renin secretion increased during diuretic administration, suggesting that the macula densa signal for renin release was also preserved in patients with relatively mild CHF.     

Immediate and short-term cardiovascular effects of fosinopril, a new angiotensin-converting enzyme inhibitor, in patients with essential hypertension.

Immediate and short-term cardiovascular effects of a new angiotensin-converting enzyme inhibitor, fosinopril, were assessed in 10 patients with mild to moderate essential hypertension. Administration of a 10 mg oral dose of fosinopril reduced mean arterial pressure (p less than 0.001) as a result of a 24% fall in total peripheral resistance (p less than 0.001). Short-term therapy (12 weeks) maintained the decrease in mean arterial pressure (p less than 0.05) by decreasing total peripheral resistance (p less than 0.01), without reflexive cardiac stimulation or expanding intravascular volume. Renal vascular resistance decreased (p less than 0.05) while renal blood flow, glomerular filtration rate and filtration fraction remained unchanged. The response pattern to mental, isometric and orthostatic stress was similarly unchanged. Left ventricular mass diminished by 11% (p less than 0.01); myocardial contractility was unaffected. Afterload was reduced (p less than 0.05), and velocity of circumferential fiber shortening and stroke volume increased (p less than 0.05). Thus, arterial pressure reduction produced by fosinopril was associated with improved systemic and renal hemodynamics and reduced left ventricular mass.     

Heterogeneity of cardiorenal characteristics in normotensive subjects

Blood pressure is a marker of elevated risk for cardiovascular disease, even within the normotensive range. The present study evaluates cardiorenal modifications observed in normotensive (<140/90 mm Hg) subjects. Using World Health Organization-International Society of Hypertension definitions, 265 normotensive subjects were categorized as having optimal (n=73), normal (n=84), and high-normal (n=108) blood pressure. Renal hemodynamics and function and cardiac morphology were evaluated by isotopic clearance techniques and ultrasonography, respectively. Urinary albumin excretion was measured in 24-hour urine collections. Body mass index and 24-hour urinary sodium (estimate of sodium intake), as well as left ventricular mass index, relative wall thickness, and glomerular filtration rate and filtration fraction, progressively increased in the optimal to high-normal groups. In contrast, effective renal plasma flow remained constant. Albuminuria was similar in all groups. Of interest, the proportion of subjects with concentric pattern of cardiac geometry (relative wall thickness > or =0.44) increased from 7% in optimal to 13% and 20% in normal and high-normal groups, respectively (P<0.05). Within this normotensive range of blood pressure, left ventricular mass index and relative wall thickness but not albuminuria were linearly correlated to systolic blood pressure; however, no correlation with diastolic blood pressure was found. In conclusion, changes in cardiac geometry and renal hemodynamics (increase in glomerular filtration rate and filtration fraction, an approximate index of glomerular pressure) that could predispose to cardiovascular morbidity and renal risk are already present in normotensive subjects with blood pressure higher than 120/80 mm Hg.     

Alpha-adducin Gly460Trp polymorphism and renal hemodynamics in essential hypertension

Previous studies have shown an association between the alpha-adducin Gly460Trp polymorphism and salt-sensitive hypertension. Not much is known about the effects of the variants of this polymorphism on renal hemodynamics and function. Therefore, we performed the present study to investigate the effect of the 460Trp allele of the alpha-adducin gene on renal hemodynamics in one hundred and seventeen essential hypertensive patients who were put on a low and high sodium diet (randomized order). On the last day of each one-week dietary period, blood pressure, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), and neurohormones were measured. Effective renal blood flow (ERBF), renal vascular resistance, and filtration fraction were calculated. ERPF, ERBF, and GFR were lower in patients homozygous for the 460Trp allele compared with patients with the Gly460Gly genotype on low sodium diet but no differences were found at the higher sodium intake. On the other hand, levels of atrial natriuretic peptide were significantly higher in patients with the Trp460Trp genotype as compared with patients with the Gly460Gly genotype on both diets. In multivariate analysis, Trp460Trp genotype, age, and mean arterial pressure were predictors of ERPF, whereas Trp460Trp genotype and age were predictors of GFR during the phase of low sodium diet. The present study shows that the Trp460Trp genotype is significantly associated with reduced renal plasma flow and glomerular filtration rate as compared with the wild-type variant.     

Effect of Antihypertensive Treatment on Cardiac and Subcutaneous Artery Structure: A Comparison Between Calcium Channel Blocker and Thiazide-Based Regimens

The effects of two antihypertensive regimens (isradipine and hydrochlorothiazide-amiloride) on the ratio between media thickness and lumen diameter of subcutaneous arteries and on left ventricular mass in essential hypertension were compared.Fifty patients, aged 46.3 ± 8 (mean ± SD) years, with newly diagnosed or poorly controlled essential hypertension were randomized to treatment with either isradipine or hydrochlorothiazide-amiloride. Atenolol and hydralazine were added in both groups as secondary and tertiary drugs, respectively, when needed for normalization of diastolic blood pressure. A subcutaneous gluteal biopsy was taken surgically before medication and again after 9 months of successful antihypertensive treatment. Two small resistance arteries were isolated from each biopsy and mounted in a Mulvany-Halpern isometric small vessel myograph. The media thickness-to-lumen diameter ratio (percentage) of the vessels was measured under standardized conditions and meaned. Left ventricular mass (LVM) index was determined by echocardiography according to the Penn convention. Ten patients were treated with isradipine as monotherapy, whereas only one patient was well controlled on diuretics as monotherapy. Mean blood pressure was reduced equally with the two regimens, from 131 ± 9 mm Hg to 101 ± 10 mm Hg with the isradipine and from 128 ± 9 mm Hg to 99 ± 7 mm Hg with the thiazide/atenolol regimen. LVM decreased significantly in both groups by 130 ± 75 g with the isradipine-based regimen and by 70 ± 53 g with the hydrochlorothiazide/atenolol-based regimen. The reduction of LVM was significantly greater on the isradipine-based regimen than on the thiazide-based regimen (P < .01). There was a significant reduction of media thickness-to-lumen diameter ratio during treatment with the isradipine-based regimen from 10.9% to 8.8% (P < .01). The reduction in the thiazide regimen was from 9.7% to 8.5%, which was not significant (P = .07).The study demonstrated significant reduction of hypertensive changes in peripheral resistance artery structure during antihypertensive treatment with an isradipine-based regimen. The thiazide/β-blocker-based regimen did not have a significant effect on the vessels. Significant reduction of LVM was achieved with both isradipine-based and thiazide/atenolol-based regimens. The reduction of LVM obtained with the isradipine-based regimen was significantly greater than that of the thiazide/atenolol-based regimen.     

Combined actions of isradipine and captopril on renal function in hypertension.

The object of this study was to test the hypothesis that the natriuretic and uricosuric effect of calcium-entry blockers could be mediated through antagonism of angiotensin II dependent intrarenal mechanisms. The antihypertensive efficacy, haemodynamic and excretional effects of superimposed calcium blockade with isradipine were investigated in seven hypertensives with unsatisfactorally controlled blood pressure with captopril 50 mg twice daily. Glomerular filtration rate (GFR) and renal plasma flow (RPF), clearances (C) of sodium (Na), potassium (K), uric acid (UA) and lithium (Li), were measured before and after a low-dose bolus of isradipine, i.v. Subsequently, measurements were repeated during constant i.v. infusion of a higher dose with definite systemic haemodynamic effects. After 4 months of combined treatment with isradipine and captopril renal investigations were carried out again. The low isradipine dose induced a slight but statistically significant increment in CNa (22% +/- 28) and heart rate (4% +/- 4), whereas no other variables changed significantly. Infusion of the high isradipine dose caused a pronounced fall in renal vascular resistance (27% +/- 14), systolic (8% +/- 2) and diastolic blood pressure (17% +/- 5). RPF increased significantly (15% +/- 18) whereas no changes were noted in GFR, filtration fraction and urinary albumin excretion rate. In spite of the pronounced fall in BP during the high dose infusion, significant increments in natriuresis (91% +/- 63) and diuresis (41% +/- 27) were induced. The natriuresis was caused by a proximal tubular action as indicated by increased CLi and CLi/GFR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of short-term administration of cromakalim on renal hemodynamics and eicosanoid excretion in essential hypertension.

Cromakalim, a novel potassium channel-activating drug, was administered for a 3-day period in eight untreated hospitalized patients with established hypertension. The fixed and single dose of 1.5 mg/day produced a significant reduction in systolic and diastolic blood pressure with a small increase in heart rate. Glomerular filtration rate was unchanged and effective renal plasma flow was slightly increased with a concomitant small decrease in filtration fraction and in renal vascular resistance. No significant change was observed in urinary prostaglandin (PG)E2, PGF2 alpha, and thromboxane B2, while 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) rose from 189 +/- 6 to 368 +/- 115 ng/day. The renal excretion of 6-keto-PGF1 alpha correlates with the modification observed in renal plasma flow, suggesting a compensatory role for prostacylin in preserving renal hemodynamics during antihypertensive therapy with cromakalim.