Acute haemodynamic effects of a new calcium antagonist, nicardipine, in man. A comparison with nifedipine

1 The acute cardiovascular response to nicardipine was investigated using non invasive techniques in normal subjects. 2 In six subjects, i.v. nicardipine in an increasing dose (0.5-20 mg) was compared with saline, under double-blind conditions. A dose related increase in heart rate and fall in blood pressure were found. Pre-ejection period (PEP) and PEP/left ventricular ejection time (LVET) ratio of the systolic time intervals were shortened in a clearly dose related manner. Total electromechanical systole index (QS2 I) was decreased and LVET index prolonged. 3 In four subjects increasing oral doses (10-40 mg) of nicardipine, administered in a randomized double-blind placebo control design, demonstrated the same pattern, marked changes being found with the 40 mg dose. 4 Comparison with nifedipine in a double-blind-placebo controlled balanced trial in six subjects confirmed that 40 mg nicardipine and 20 mg nifedipine exhibited similar effects. Maximum response was reached between 0.5 and 1.5 h, and changes in some cardiovascular variables were still evident at 3 h.     

The effects of nicardipine on sodium and calcium metabolism in hypertensive patients: a chronic study

There is evidence in the literature that calcium entry blockers are able to affect calcium-dependent hormone secretion and therefore can influence sodium and calcium metabolism. We have studied in 18 mild to moderate hypertensives (27-65 yrs) the effects of chronic treatment with nicardipine, a dihydropyridine derivative, vs placebo on: 1) renin-angiotensin-aldosterone axis; 2) parathyroid hormone and calcium metabolism; 3) daily sodium and calcium urinary excretion. After a 2-week placebo wash-out when any antihypertensive treatment was withdrawn, patients were kept on a well balanced normocaloric diet without salt intake restriction. Blood pressure, plasma renin and serum aldosterone after a 1-hour standardized walk, serum PTH, serum and 24-hour urinary Na, K, Ca, P, Mg were measured. Thereafter patients were randomly and blindly given nicardipine 20 mg tid or placebo tablet tid for 2 months. At the end of this period the same measurements were repeated. Blood pressure significantly dropped during nicardipine (from 165/96 +/- 19/9 vs 150/88 +/- 16/9 mm Hg P less than .05) without change in heart rate. No change was observed on placebo. Plasma renin, serum aldosterone, serum parathyroid hormone and serum and urinary electrolytes did not change during active and placebo treatment. The results of this study suggest that chronic nicardipine does not affect hormone secretion.     

Acute and chronic effects of T-1032, a novel selective phosphodiesterase type 5 inhibitor,on monocrotaline-induced pulmonary hypertension in rats

We examined the hemodynamic property of T-1032 (methyl 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridylmethoxy)-4-(3,4,5-trimethoxy-phenyl)-3-isoquinoline carboxylate sulfate), a novel selective phosphodiesterase type 5 (PDE5) inhibitor, and evaluated the chronic effect of T-1032 on cardiac remodeling and its related death in monocrotaline (MCT)-induced pulmonary hypertensive rats. T-1032 (1, 10, 100 micro g/kg, i.v.) significantly reduced mean arterial pressure (MAP) and right ventricular systolic pressure (RVSP) without a change in heart rate. The change in RVSP was more potent than that in MAP with 1 micro g/kg T-1032 treatment (RVSP: -8.2+/-1.2%, mean arterial pressure: -5.7+/-1.2%), and reductions in RVSP and MAP reached a peak at doses of 1 and 10 micro g/kg, respectively. In contrast, nitroglycerin (0.1, 1, 10 micro g/kg, i.v.) and beraprost (0.1, 1 micro g/kg, i.v.) did not cause a selective reduction in RVSP at any dose. When T-1032 (300 ppm in diet) was chronically administered, it delayed the death, and significantly suppressed right ventricular remodeling (T-1032-treated: 0.318+/-0.021 g, control: 0.401+/-0.013 g, p<0.05). Our present results suggest that T-1032 selectively reduces RVSP, and resulting in the suppression of right ventricular remodeling with a delay of the death in MCT-induced pulmonary hypertensive rats.     

Acute systemic and regional hemodynamic effects of felodipine, a new calcium antagonist, in conscious renal hypertensive rabbits

Using the radioactive microsphere technique, we studied the acute systemic and regional hemodynamic effects of felodipine (10, 30, and 100 nmol/kg, i.v.) in conscious renal hypertensive rabbits. A dose-dependent decrease in arterial blood pressure was observed after felodipine administration, accompanied by tachycardia. Cardiac output increased significantly after the third felodipine dose. Thus, the hypotensive effect of the drug resulted from a reduction in total peripheral resistance. An increase in blood flow to the heart was measured after felodipine. However, probably secondary to the reduction in diastolic perfusion time, a decrease in the endocardial/epicardial blood flow ratio was noticed in the left ventricular wall. The drug also enhanced the blood supply to the brain, the gastrointestinal tract, and, at higher doses, to the skeletal muscles while blood flow to the kidneys and the bones remained unchanged. After the highest dose of felodipine, a significant decrease in the blood flow to the skin was measured. With the exception of the cutaneous vascular bed, felodipine caused a rather generalized peripheral vasodilatation. In conclusion, felodipine appears to be a very effective antihypertensive agent. However, the stimulation of the heart and the unfavorable regional blood flow distribution in the left ventricular wall illustrate the negative aspects of single treatment with this arterial vasodilator.     

Long-term renal effects of isradipine, a calcium entry blocker, in essential hypertension

The long-term effects (9 weeks) on renal hemodynamics of the new calcium entry blocker isradipine (PN 200-110) were assessed in 20 middle-aged male patients with essential hypertension. The study was double-blind placebo-controlled with a crossover design. Isradipine or placebo tablets were titrated from 2.5, 5, and 7.5 mg b.i.d. every 3rd week to achieve a diastolic blood pressure of less than or equal to 90 mm Hg. The renal parameters were assessed 2-4 h after dosing. Despite a decrease in diastolic blood pressure (91 vs. 104 mm Hg, p less than 0.001) the renal plasma flow increased (465 vs. 394 ml/min, p less than 0.05). The glomerular filtration rate was unchanged and the filtration fraction was reduced (0.21 vs. 0.23, p less than 0.05). The plasma renin activity increased (0.71 vs. 0.51, p less than 0.05). The patients probably did not retain sodium because the body weight was unchanged. Rather, long-term treatment with isradipine was associated with a repetitive postdose increase in natriuresis (0.45 vs. 0.34 mmol/min, p = 0.06).     

Antihypertensive and renal effects of nicardipine

Both the acute blood pressure lowering and renal effects of the calcium antagonist nicardipine and those after 1 week's treatment were investigated in 10 normotensive volunteers and in 10 patients with mild to moderate essential hypertension. After 1 week of placebo, nicardipine was administered orally for 1 week (20 mg three times daily), Investigations, done on the first and last day of nicardipine treatment were compared with those on the last day of placebo. During water loading, nicardipine increased urinary volume and urinary excretion of sodium significantly after 1 week nicardipine treatment. In the normotensive group the natriuretic effect was caused by a decrease of fractional proximal and distal reabsorption of sodium. In the hypertensive group the natriuresis was achieved mainly by an increase of the rate of glomerular filtration (GFR) and also by a slight distal effect. Our results show that nicardipine had natriuretic effects. There were trends suggesting that the renal effects may differ between patients with essential hypertension and normotensive volunteers, but the findings might also be related to differences in age between the groups.     

Hemodynamic, renal, and humoral effects of the calcium entry blocker nicardipine and converting enzyme inhibitor captopril in hypertensive type II diabetic patients with nephropathy

We compared the effect of nicardipine, a dihydropiridine derivative calcium entry blocker (CEB), with that of captopril (CAP), a converting-enzyme inhibitor (CEI), and that of the two drugs combined, on blood pressure (BP), heart rate (HR), and renal function in 12 hypertensive type II diabetic outpatients with nephropathy (persistent proteinuria greater than 500 mg/24 h) according to a 2 x 2 factorial design. For 4-week treatments, the patients received nicardipine (NIC) 20 mg t.i.d., CAP 50 mg b.i.d., NIC plus CAP, and matched placebo. Each active treatment significantly reduced BP, with an additive effect of NIC and CAP combined versus either drug alone. HR did not change. Effective renal plasma flow (RPF) and glomerular filtration rate (GRF) were unmodified, but renal vascular resistances (RVRs) were significantly reduced by the three active treatments. Filtration fraction (FF) did not change with NIC or with NIC plus CAP and was significantly reduced with CAP. Urinary albumin excretion (UAE) was significantly reduced by each active treatment to a similar extent. Plasma renin activity (PRA) increased significantly with NIC plus CAP only and did not change when the drugs were administered singly. Plasma aldosterone, glucose, potassium, fructosamine, and urinary sodium and volume did not change during the trial. We conclude that the two drugs singly and combined are useful for treatment of hypertensive non-insulin-dependent diabetes (NIDD) patients with persistent proteinuria.     

Influence of nicardipine on renal hemodynamics and segmental tubular reabsorption of sodium in humans

Calcium antagonists induced natriuresis in humans as well as in experimental animals. However, the tubular sites involved have not been precisely evaluated in humans. Using both free-water and lithium clearance, the latter as a marker of absolute sodium distal delivery, we measured segmental tubular movement of sodium before and after acute intravenous (i.v.) nicardipine administration 2.5 mg as a single dose in eight healthy normotensive volunteers on normal sodium diet. Nicardipine decreased slightly but significantly the mean arterial pressure (MAP) (from 98.9 +/- 8.8 to 91.8 +/- 9.2 mm Hg; p less than 0.01) and the renal vascular resistance (from 6,142 +/- 1,082 to 5,578 +/- 893 dynes.s/cm5 . 1.73 m2; p less than 0.05), whereas the glomerular filtration rate (GFR), the renal plasma flow (RPF), and the filtration fraction (FF) were unchanged. Nicardipine acutely increased the absolute and the fractional excretion of sodium (from 282 +/- 60 to 427 +/- 152 mumol/min.1.73 m2; p less than 0.01 and from 0.015 +/- 0.004 to 0.023 +/- 0.013; p less than 0.01, respectively). When assessed by either lithium clearance or free-water clearance, both proximal and distal fractional reabsorption of sodium were decreased by nicardipine. These results indicate that the nicardipine-induced natriuretic effect is due to decreased sodium reabsorption in both proximal and distal sites of the nephron. Shifts in segmental tubular sodium reabsorption obtained from either free-water or lithium clearance were directionally similar but quantitatively different.     

First-step treatment of mild to moderate uncomplicated essential hypertension by a new calcium antagonist: nicardipine

Nicardipine, a new calcium antagonist, was tested in a 14-week double-blind trial including 15 outpatients with uncomplicated essential hypertension. They were randomly assigned to nicardipine (20-30 mg three times daily) or placebo as first-step treatment. When necessary but always after a minimum of 4 weeks, pindolol (15 mg/day) was combined with nicardipine or placebo. At the end of step 1 (85 +/- 6 days with nicardipine vs. 58 +/- 6 days with placebo, p less than 0.01), nicardipine induced larger drops in supine systolic and diastolic blood pressure (SBP and DBP) than the placebo (21 +/- 2.5 vs 1.4 +/- 3 mm Hg, p less than 0.001, and 13 +/- 2 vs. 3.5 +/- 1.5 mm Hg, p less than 0.001, respectively). In the nicardipine group (n = 57), 53% of patients had controlled blood pressure (SBP less than 160 mm Hg and DBP less than 95 mm Hg) versus 17% in the placebo group (n = 47), p less than 0.001. There was no significant correlation between the decrease in blood pressure and the age of patients. The most common side effects in the nicardipine group were flushes (12%), headache (8%), ankle edema (5%), and asthenia (4%). When blood pressure was not brought under control and pindolol was prescribed as the second-step treatment, the nicardipine group (n = 52) displayed larger drops in SBP and DBP than the placebo group (n = 40) (27 +/- 5 vs. 15 +/- 3 mm Hg, p less than 0.01, and 18 +/- 1 vs. 9 +/- 2 mm Hg, p less than 0.001, respectively). These results show that a calcium antagonist is useful for first-step treatment of hypertension.     

Acute and chronic effects of nifedipine in arterial hypertension

Summary Sublingual administration of nifedipine 10 mg to 11 patients and 20 mg to 6 patients with arterial hypertension caused a rapid and significant decrease in blood pressure in both groups. The average maximal reductions in the two groups were 21/16 mm Hg and 27/21 mm Hg. A concomitant rise in heart rate was found. Forearm blood flow showed a significant increase and the calculated vascular resistance a significant decrease 15–60 min after administration of both the 10 mg and the 20 mg doses. There was a negative correlation between basal vascular resistance and the maximal change of this parameter (r=–0.72, p<0.01). Plasma concentrations of nifedipine showed considerable individual variation, with slow absorption in some patients, which indicated failure of sublingual absorption in them. The difference between the mean plasma concentration in the two dose groups was statistically significant after 45 min. A negative correlation was present between the plasma concentration of nifedipine and the observed change in calculated vascular resistance (r=–0.74 at t=30 min). Treatment of 10 hypertensive patients with nifedipine 30–60 mg daily for 6 weeks reduced mean blood pressure from 175/115 mm Hg to 151/96 mm Hg (p<0.001). Heart rate and forearm blood flow rose, whereas the forearm vascular resistance showed a significant decrease. Side effects of a sensation of heat and reddening of face were noted in some patients. It is suggested that nifedipine may be useful both in the acute and chronic treatment of arterial hypertension.     

Effects of KB-2796, a new diphenylpiperazine calcium antagonist, on renal hemodynamics and urine formation in anesthetized dogs.

The effects of KB-2796, a new calcium antagonist with a diphenylpiperazine moiety, on renal hemodynamics and urine formation were investigated in anesthetized dogs. Intravenous infusion of KB-2796 (10, 30, and 100 micrograms/kg/min) decreased mean blood pressure (MBP) and renal vascular resistance (RVR) in a dose-dependent manner, but did not change renal blood flow (RBF). At the highest dose, glomerular filtration rate (GFR) and urine flow (UF) tended to decrease. Nicardipine (0.1, 0.3, and 1 microgram/kg/min) also dose-dependently decreased MBP, RVR, GFR, and UF. When KB-2796 was infused into the renal artery at lower doses of 3 and 10 micrograms/kg/min, UF and urinary excretion of electrolytes increased without a significant change in RBF and GFR. Intrarenal infusion of KB-2796 at 30 micrograms/kg/min and nicardipine at 0.3 microgram/kg/min produced a significant increase in GFR, RBF, UF, urinary excretion of electrolytes, and renin secretion rate. These results suggest that KB-2796 administered intrarenally exerts a diuretic action via tubular effects and the alteration of renal hemodynamics. However, its diuretic action might be masked by diminished urine formation via a reflex activation of the sympathetic nerves and/or via a reduction of renal perfusion pressure when it is administered systemically.     

Effects of cromakalim on renal hemodynamics and function in dogs: comparison with nicardipine.

The effects of cromakalin, a potassium channel opener, on renal hemodynamics and renal function were investigated in pentobarbital-anesthetized dogs. Intrarenal infusion of cromakalim at 0.5 micrograms/kg/min resulted in significant increases in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and renin release. The urinary excretion rate of sodium increased by the same proportion as that of calcium. Free water reabsorption rate/osmolar clearance did not significantly change throughout the experiments. These data suggest that cromakalim did not inhibit sodium transport at the medullary portion of the ascending limb of Henle's loop and may have increased the delivery of sodium to Henle's loop. Intrarenal infusion of nicardipine increased RBF, GFR, urine flow, and the urinary excretion of electrolytes (Na, K, and Ca). The renal effects of cromakalim were very similar to those of nicardipine. Cromakalim was superimposed on a nicardipine infusion of a maximal effective dose. Superimposition of cromakalim to the nicardipine infusion did not cause any additional changes in renal hemodynamics and renal function. These data suggest that cromakalim and nicardipine exert their effects on renal hemodynamics and function via the same pathway.     

Comparative effects on blood pressure and regional hemodynamics of nicardipine and captopril.

This randomized, double-blind, crossover study was aimed at detecting efficacy differences in blood pressure control and peripheral circulation in cerebral aortic and femoral districts of slow-release nicardipine, 40 mg, and captopril, 50 mg, given twice daily to 20 primary hypertensive patients (9 male, 11 female; age range 33-60 years) for a period of 4 weeks for each treatment. Blood flow velocities in the aorta, common carotid artery, internal carotid artery, middle cerebral artery, and common femoral artery were noninvasively measured using a 2.0- or 5-MHz Doppler probe. Systolic blood pressure fall was similar with nicardipine (from 156 +/- 12 to 139 +/- 8 mm Hg, p less than 0.001) and captopril (from 158 +/- 13 to 146 +/- 13 mm Hg, p less than 0.001) while significant efficacy difference (p less than 0.005) in diastolic pressure control was detected (from 104 +/- 6 to 91 +/- 8 mm Hg, p less than 0.001 with nicardipine and from 102 +/- 6 to 98 +/- 7 mm Hg with captopril). Regarding regional hemodynamics, nicardipine increased (from 119 +/- 24 to 133 +/- 27 cm/s), and captopril did not affect systolic velocity in the aorta (difference between final data, p less than 0.03). In the common carotid artery systolic velocity was increased solely by nicardipine. No significant changes were detected in the other vessels explored.(ABSTRACT TRUNCATED AT 250 WORDS)     

LAAE-14, a new in vitro inhibitor of intracellular calcium mobilization,modulates acute and chronic inflammation

A new lipidic acid-amido ether derivative (LAAE-14) able to reduce dose-dependently the calcium increases mediated either by calcium ionophore ionomycin, by the endoplasmic reticular Ca(2+)-ATPase inhibitor thapsigargin, or by the chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), in human neutrophils as well as in murine peritoneal macrophages, but not ATP, has been evaluated as a potential anti-inflammatory drug. This compound attenuated leukocyte activation by means of its inhibitory effect on the respiratory burst elicited in both types of cells by 12-O-tetradecanoyl phorbol 13-acetate, by inhibition of the degranulation process induced by cytochalasin B+fMLP or cytochalasin B+platelet activating factor, as well as by reduction of leukotriene B(4) synthesis induced by the calcium ionophore A23187. In addition, in zymosan-stimulated mouse peritoneal macrophages LAAE-14 caused a potent inhibition of nitrite and prostaglandin E(2) production. This compound exerted acute and chronic anti-inflammatory effects by oral route, that may be related with several mechanisms such as attenuation of leukocyte activation, inhibition of inducible nitric oxide synthase, cyclo-oxygenase-2 and cytosolic phospholipase A(2) expression as well as reduction in tumour necrosis factor-alpha production. Its anti-inflammatory profile is clearly correlated with its behavior as inhibitor of intracellular calcium mobilization. The profile and potency of this compound may have relevance for the inhibition of the inflammatory response at different levels and may represent a new approach to the development of new anti-inflammatory drugs.     

Acute and chronic effects of vinpocetine on cerebral hemodynamics and neuropsychological performance in multi-infarct patients

A double-blind, prospective, randomized, placebo-controlled clinical trial was carried out to test the acute and long-term hemodynamical and beneficial cognitive effects of the vasoactive agent vinpocetine on patients suffering from multiple cerebral infarcts by means of functional transcranial Doppler examinations and by neuropsychological tests. Twenty-six patients (17 men, 9 women) with multiple cerebral infarctions, aged between 50 and 83 years (mean age+/-SD=63.4+/-9.39 years) were examined, 14 of whom received vinpocetine and 12 placebo. The functional transcranial Doppler included breath-holding tests, finger movement, word fluency, and picture-discrimination tasks. Twenty-five patients were assessed by neuropsychological battery. No serious side effect was found in the vinpocetine group. The flow velocities were significantly lower in the acute phase after breath holding in the vinpocetine group than in the placebo group. Three months later, the vinpocetine patients did not show any significant worsening in digit span backward test, while the placebo group did. No other significant differences in the neuropsychological test could be detected between the treatment and the placebo groups. Longer lasting and higher dosage of vinpocetine therapy is suggested to prove its potential effect.     

Perindopril, a new converting enzyme inhibitor: systemic and regional hemodynamics and sympathoinhibitory effects in spontaneously hypertensive rats

The effects of a new converting enzyme inhibitor, perindopril (5 mg/kg p.o. q.d. for 8 days), on systemic and regional hemodynamics, as well as its interferences with the sympathetic nervous system at the cardiovascular level, were investigated in nonbinephrectomized and in binephrectomized spontaneously hypertensive rats (SHRs). Perindopril abolished plasma converting enzyme activity and lowered arterial blood pressure (BP) without affecting heart rate. Cardiac index (microspheres) was not drug affected; thus, the reduction in BP was due to a decrease in total peripheral resistance which was shown to be homogenous, since all investigated vascular resistances were reduced to the same extent. In nonbinephrectomized, pithed SHRs, perindopril decreased BP and renal and hindlimb vascular resistances (pulsed Doppler). In addition, perindopril exerted a sympathoinhibitory effect as evidenced by (a) a reduction in the systemic vasopressor and regional vasoconstrictor responses to the alpha 1-adrenoceptor agonist, cirazoline, and especially to the alpha 2-adrenoceptor agonist UK 14.304; and (b) a decrease in the systemic pressor and in the hindlimb vasoconstrictor responses to spinal cord stimulation. In binephrectomized, pithed SHRs, perindopril no longer decreased BP; however, whereas its sympathoinhibitory effect versus alpha-adrenoceptor agonists was abolished, that versus spinal cord stimulation persisted. These results indicate that (a) perindopril lowers BP in SHRs by a renal-dependent mechanism; (b) perindopril exerts in SHRs a sympathoinhibitory effect versus alpha-adrenoceptor agonists and spinal cord stimulation; (c) the sympathoinhibitory effect of perindopril versus alpha-adrenoceptor agonists is postjunctional and kidney dependent; and (d) the sympathoinhibitory effect of perindopril versus spinal cord stimulation is possibly prejunctional in its mechanism and does not require the presence of the kidneys.     

Effects of the calcium antagonist nicardipine on renal function and renin release in dogs

The effects of nicardipine, classed as a calcium antagonist, on renal hemodynamics, renal function, and renin release were investigated in pentobarbital-anesthetized dogs. Intrarenal infusion of this drug at a rate of 5 micrograms/min in both hydrated and hydropenic dogs resulted in a significant increase in renal blood flow, glomerular filtration rate, urine flow, and renin release, with a significant fall in systemic blood pressure. The intrarenal blood flow as measured by the microsphere method indicated a greater increase in flow rate in the juxtamedullary than in the superficial area. During nicardipine infusion, free water reabsorption rate (TcH2O) in hydropenic dogs or free water production (CH2O) in hydrated dogs increased in proportion to the urine flow. Neither TcH2O/CH2O nor CH2O/osmolar clearance were significantly changed throughout the experiments. These data suggest that nicardipine did not inhibit sodium transport at the medullary portion of the ascending limb of Henle, and that the increase in GFR might induce an enhancement of the delivery of sodium to the Henle loop. In addition, an intrarenal hemodynamic alteration may be one possible mechanism involved in the diuretic action of nicardipine. Calcium-antagonistic actions of nicardipine may account for the changes in renal parameters.     

Effects of the new angiotensin-converting enzyme inhibitor imidapril on renal hemodynamics and function in anesthetized dogs.

The effects of a new angiotensin-converting enzyme (ACE) inhibitor, imidapril hydrochloride ((-)-(4S)-3-[(2S)-2- [[(1S)-1-ethoxycarbonyl-3-phenylpropyl]amino]propionyl]- 1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) and of its active metabolite, 6366 A (CAS 89371-44-8) on renal function were studied in anesthetized dogs and compared to the effects of enalapril and its active metabolite, enalaprilat. Intravenous (i.v.) administration of 6366 A at 30 micrograms/kg strongly inhibited angiotensin I-induced renal vasoconstrictive and pressor responses. 6366 A promptly lowered blood pressure and renal vascular resistance, and caused clear increases in renal blood flow and glomerular filtration rate. It also increased urine volume and urinary excretion of sodium and chloride. These renal effects were also produced by intraduodenal (i.d.) administration of 2 mg/kg of imidapril. However, the effects of i.d. imidapril began later, developed gradually and reached a plateau after 2 to 3 h. Enalaprilat (30 micrograms/kg i.v.) and enalapril (2 mg/kg i.d.) had renal effects similar to 6366 A and imidapril. In conclusion, the ACE inhibitor imidapril has beneficial effects on renal function via its active metabolite, and the effects appear to be essentially identical to those of enalapril.     

Effects of CV-4093, a new dihydropyridine calcium channel blocker, on renal hemodynamics and function in stroke-prone spontaneously hypertensive rats (SHRSP)

Renal effects of CV-4093, a newly developed dihydropyridine calcium channel blocker, were examined using anesthetized stroke-prone spontaneously hypertensive rats, and the findings were compared with those of nicardipine. An intravenous injection of CV-4093 (2 micrograms/kg) produced long-lasting hypotension with a slow-onset accompanied by moderate renal vasodilation. There were no appreciable alterations in glomerular filtration rate (GFR) and urine formation, except that urine flow (UF) increased significantly during the first 10 min after injection. When CV-4093 was administered at 10 micrograms/kg, the hypotensive action was markedly augmented. Eighty minutes after the injection, a decrease in mean arterial pressure of about 45 mmHg was observed. Simultaneously, renal blood flow increased significantly from the control value of 5.76 +/- 0.46 ml/g.min to 6.94 +/- 0.28 ml/g.min. Renal vascular resistance decreased immediately after the injection, and the response lasted for over 3 hr, thereby indicating the marked and sustained renal vasodilating effect of CV-4093. GFR was constant throughout the experiment, but UF and urinary excretion of sodium were increased significantly. Fractional excretion of sodium was also elevated, thereby suggesting an inhibitory action of CV-4093 on renal tubular reabsorption of sodium. Nicardipine at a dose of 10 micrograms/kg, a dose producing an effective hypotensive action, caused no significant increases in RBF and urine formation. The renal vasodilating and diuretic actions of CV-4093 may provide a beneficial effect in the treatment of hypertension.