Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nitrendipine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1991

Stereoselective pharmacokinetics of oral and intravenous nitrendipine in healthy male subjects.

1. Stereoselectivity in the pharmacokinetics of nitrendipine was investigated by reanalysing plasma samples of a previously published study (Soons et al., 1989). 2. Racemic nitrendipine was administered intravenously (40 micrograms kg-1) and orally, both as plain tablet (20 mg) and in an osmotic pump device (40 mg Osmet) to nine healthy male subjects. Nitrendipine enantiomers were measured with a stereoselective assay. 3. Upon oral administration (tablet) the bioavailability of (S)-(-)-nitrendipine (13.4% +/- 5.6%) was 75% (50% - 98%) higher than that of (R)-nitrendipine (7.9% +/- 4.0%) (mean +/- s.d. (95% confidence interval)). Values of AUC and Cmax for (S)-nitrendipine were 90% (55% - 121%) and 77% (51% - 100%) higher respectively, than those for (R)-nitrendipine. Similar results were obtained with the osmotic system. 4. The clearance of intravenously administered (S)-nitrendipine was slightly (7%) lower than that of (R)-nitrendipine, but elimination half-lives and volumes of distribution were similar. 5. The difference in disposition of nitrendipine enantiomers is most likely related to a difference in activity of the cytochrome P-450 system towards the enantiomers, giving rise to a two-fold difference in first-pass elimination. 6. Stereoselectivity in the first pass metabolism of nitrendipine exhibited little intersubject variability and therefore is not a major factor in the wide variability in systemic availability of the more-potent (S)-enantiomer.

Administration, Oral↗
PubMed2003

Improvement of dissolution and bioavailability of nitrendipine by inclusion in hydroxypropyl-beta-cyclodextrin.

A significant increase in solubility and dissolution rate of nitrendipine, a slightly soluble calcium channel blocker, was achieved by inclusion complexation with hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The inclusion complex was prepared by solvent evaporation method and characterized by phase solubility method, x-ray diffractometry, infrared spectroscopy, and differential scanning calorimetry. The solubility of nitrendipine increased linearly as a function of HP-beta-CD concentration, resulting in AL-type phase solubility diagram which revealed a formation of inclusion complex in a molar ratio of 1:1, with the apparent association constant of 108.3M(-1). The in vitro dissolution rate of nitrendipine in pH 7.4 phosphate buffer was in the order of inclusion complex, physical mixture, and nitrendipine powder. These three different forms of nitrendipine were administered orally to rats with a dose of 10 mg/kg equivalent to nitrendipine. The AUC of inclusion complex was significantly larger than that of nitrendipine powder. Tmax of inclusion complex was significantly shorter and Cmax was significantly higher than those of nitrendipine powder. Cmax of physical mixture was higher than that of nitrendipine powder. Tmax of physical mixture, however, remained the same. The results indicated that the bioavailability of nitrendipine could be improved markedly by inclusion complexation, possibly due to an increased dissolution rate.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1988

Effects of nitrendipine and cilazapril alone or in combination on hemodynamics and regional blood flows in conscious spontaneously hypertensive rats.

Nitrendipine and cilazapril are two new antihypertensive drugs with different mechanisms of action. Nitrendipine is a calcium antagonist of the dihydropyridine class which decreases directly the smooth muscle tone. Cilazapril is a new long-lasting inhibitor of angiotensin-converting enzyme which suppresses the peripheral vasoconstrictor effect of angiotensin I by inhibiting its transformation in angiotensin II. The goal of the present study was to assess the effects on hemodynamics and regional blood flows (measured with radioactive microspheres) of cilazapril and nitrendipine given alone or in combination. Cilazapril (3 mg/kg) and nitrendipine (0.3 mg/kg) were given intravenously to conscious spontaneously hypertensive rats first alone, then in combination. Both cilazapril and nitrendipine decreased mean arterial pressure to the same extent. Cilazapril increased regional blood flow only in the kidney without changing total cardiac output. In contrast, nitrendipine increased regional blood flow in nearly every organ and markedly enhanced total cardiac output. Cilazapril redistributed the cardiac output distribution toward the kidney, and nitrendipine did not change the cardiac output distribution. The combination of both nitrendipine and cilazapril produced a stronger antihypertensive effect than each drug alone. The peripheral vasodilatation with the combination was not as marked as with nitrendipine alone but was associated with the same redistribution of the cardiac output toward the kidney as with cilazapril. We conclude that after acute intravenous administration the combination of cilazapril and nitrendipine produced hemodynamic effects which cannot be induced by each drug used alone. Such a therapeutic profile may be useful in patients with high blood pressure or heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Nitrendipine and the humoral control of sodium homeostasis.

1. Nine healthy volunteers received 10 mg nitrendipine or placebo orally in random order. 2. In the subsequent 5 h urinary sodium excretion was 20% higher after nitrendipine, without any significant difference between the volume of urine excreted after nitrendipine or placebo. Mean blood pressure fell by 5 mm Hg (P less than 0.001), and mean heart rate increased by 5 beats min-1 (P less than 0.01) after nitrendipine but did not change after placebo. 3. These changes were accompanied by a significant elevation in plasma renin activity (P less than 0.001). A fall in plasma aldosterone following placebo appeared to be attenuated by nitrendipine. Plasma noradrenaline increased to a peak 3 h after nitrendipine administration (P less than 0.05) but did not change following placebo. A fall in the excretion of 6-keto PGF1 alpha following placebo was attenuated by nitrendipine. The total excretion of 6-keto PGF1 alpha after nitrendipine was significantly greater (P less than 0.05) than after placebo but not difference in the total excretion of PGE2 was detected. Nitrendipine did not affect urinary kallikrein excretion. 4. The natriuretic action of nitrendipine is not mediated by the kallikrein-kinin system, but may be related to changes in renal prostaglandins.

Adult↗
PubMed1991

Pharmacokinetics, bioavailability, metabolism and acute and chronic antihypertensive effects of nitrendipine in patients with chronic renal failure and moderate to severe hypertension.

1. The pharmacokinetics, bioavailability, metabolism and antihypertensive effects of nitrendipine have been studied in 12 patients with impaired renal function and moderate to severe hypertension. The drug was administered simultaneously by the i.v. [13C4] and oral (commercial tablet 20 mg) routes. 2. No differences in the pharmacokinetic parameters were observed between the two routes of administration. The systemic clearance after i.v. administration in patients with renal impairment (18.2 +/- 6.1 ml min-1 kg-1) was similar to that observed in healthy volunteers. Despite complete absorption of drug from the tablet the bioavailability of the parent compound was 21.2 +/- 12.5%. Cumulative urinary excretion of nitrendipine metabolites was correlated with the creatinine clearance (r = 0.946). 3. Significant reductions in mean arterial blood pressure (mean: 23.6%) at the end of the nitrendipine infusion and after oral administration of 20 mg (mean: 17.5%) were observed. The blood pressure lowering effect of nitrendipine could be correlated within individuals with serum nitrendipine concentrations using a log linear model. 4. Following 4 weeks of therapy an average dose of 77 mg nitrendipine day-1 was required to achieve a systolic blood pressure below 160 mm Hg or a diastolic blood pressure below 90 mm Hg. The reduction in blood pressure during multiple dosing was related to the nitrendipine steady-state concentration. There was a significant relationship between the nitrendipine bioavailability and the dose required for sufficient blood pressure control. 5. No accumulation of nitrendipine caused by impaired renal function was observed during multiple dosing. Thus, no reduction of the nitrendipine dose in patients with renal impairment is necessary.

Adult↗
PubMed1994

Combination treatment of enalapril with nitrendipine in rats with renovascular hypertension.

We have recently shown that treatment with the calcium channel blocker nitrendipine may aggravate albuminuria and glomerular injury in rats with two-kidney, one clip renovascular hypertension if arterial blood pressure is not reduced. To test whether nitrendipine also exerts its adverse renal effects when normotension is achieved, we examined the effect of combined therapy with nitrendipine and the converting enzyme inhibitor enalapril on blood pressure, albuminuria, glomerular filtration rate, and morphology of the nonclipped kidney. Rats treated with enalapril alone or in combination with the diuretic hydrochlorothiazide or rats treated with nitrendipine alone served as controls. Therapy was started 6 weeks after clipping of one renal artery. Nitrendipine alone did not reduce blood pressure but significantly increased albuminuria, diuresis, glomerular filtration rate, and glomerular volume and injury compared with untreated hypertensive controls. Increase of glomerular filtration rate, diuresis, and albuminuria was reversible after withdrawal of nitrendipine. Treatment with enalapril alone decreased blood pressure significantly but not to normotensive levels and was without significant effect on albuminuria and glomerular morphology. The combination of nitrendipine and enalapril reduced blood pressure to normotensive levels and not only prevented the increase of glomerular volume, glomerular filtration rate, diuresis, and albuminuria caused by nitrendipine alone but furthermore improved glomerular injury and albuminuria to levels not significantly different from normotensive controls. Enalapril in combination with the diuretic had similar beneficial effects on blood pressure, albuminuria, and glomerular injury. These data demonstrate that the adverse effects of nitrendipine monotherapy on glomerular structure and function can be prevented by the combination of nitrendipine and enalapril when blood pressure is normalized.

Albuminuria↗
PubMed1988

[Effects of nitrendipine on cardiovascular systems].

Cardiovascular effects of nitrendipine were examined in anesthetized dogs, blood-perfused canine papillary muscles and isolated arteries. In anesthetized dogs, nitrendipine by intravenous (0.3-10 micrograms/kg) or intraduodenal (0.1 mg/kg) administration lowered blood pressure and increased coronary and vertebral blood flow. Nitrendipine also decreased the difference in oxygen concentrations between arterial and coronary sinus blood, which indicates that nitrendipine increased the oxygen supply to the heart. Myocardial oxygen consumption was slightly increased at a low dose (3 micrograms/kg, i.v.) accompanied with a small increase in max dP/dt, but was decreased at high doses (30-100 micrograms/kg, i.v.). A negative inotropic effect was observed in blood-perfused canine papillary muscles. However, nitrendipine is thought to be highly vasoselective because much higher doses were required to decrease the myocardial contraction than to increase the coronary blood flow. Furthermore, nitrendipine suppressed the contraction induced by KCl, acetylcholine, histamine, norepinephrine, 5-hydroxytryptamine and prostaglandin F2 alpha of porcine coronary arteries, and the rhythmic contraction induced by 3,4-diaminopyridine of canine coronary arteries. In isolated rabbit aortic preparations, nitrendipine strongly inhibited the KCl-induced contraction, but not the phenylephrine-induced contraction. These effects of nitrendipine were almost similar to those of nifedipine. It is suggested that nitrendipine decreases afterload (blood pressure), increases the blood flow and oxygen supply to the heart, and inhibits coronary spasm, which is due to the calcium antagonistic effect. Nitrendipine may be useful for the treatment of ischemic heart diseases.

Animals↗
PubMed1985

Short term and long term effects of beta-adrenergic effectors and cyclic AMP on nitrendipine-sensitive voltage-dependent Ca2+ channels of skeletal muscle.

The effects of short term stimulation of beta-adrenergic receptors and elevations in intracellular cyclic AMP on nitrendipine-sensitive voltage-dependent Ca2+ channels of skeletal muscle cells in vitro has been studied using both the 45Ca2+ flux technique and [3H] nitrendipine-binding experiments. Isoproterenol increased the nitrendipine-sensitive 45Ca2+ influx under depolarizing conditions. The effects of isoproterenol were additive to those of depolarization and were antagonized by alprenolol. Half-maximal inhibition of 45Ca2+ influx induced both by depolarization and by isoproterenol occurred at a nitrendipine concentration of 1 nM. Treatments that resulted in an increased level of intracellular cyclic AMP, such as treatment with 1-methyl-3-isobutylxanthine, theophylline, dibutyryl cyclic AMP, or 8-bromocyclic AMP also resulted in an increased rate of 45Ca2+ entry via nitrendipine-sensitive Ca2+ channel. In contrast, long term treatment of myotubes in culture with isoproterenol and other compounds that increased intracellular cyclic AMP led to a large increase in the number of nitrendipine receptors. This increase was accompanied by a 4-10-fold decrease in the affinity of the receptors for nitrendipine. Alprenolol inhibited the long term effects of isoproterenol. In vivo treatment of 7-day-old chicks with reserpine and alprenolol produced a decrease in the number of skeletal muscle nitrendipine receptors. This decrease in receptor number was accompanied by an increase in the affinity of nitrendipine for its receptor by a factor of 4 to 5. These effects on the nitrendipine receptor were prevented by simultaneous injection of isoproterenol. The results are discussed in relation to the role of beta-adrenergic receptors and intracellular cyclic AMP in the regulation of skeletal muscle Ca2+ channels.

1-Methyl-3-isobutylxanthine↗
PubMed1989

[Effect of nitrendipine on isolated uterus and other smooth muscles of the rat].

Increasing concentrations of nitrendipine were found to inhibit various types of muscular activation (electrical stimulation, acetylcholine, oxytocin, potassium chloride), as well as the spontaneous rhythmic activity of the isolated rat uterus. The degree of the inhibitory effect of nitrendipine depends on the type of activation. Nitrendipine showed an exceptionally high efficacy in inhibiting contractions induced by electrical stimulation and of spontaneous rhythmic activity. For inhibition of these contractions even osmolar concentrations of nitrendipine were sufficient. The relaxant effect of nitrendipine depended on the concentration of extracellular calcium and the time of incubation of nitrendipine in the bathing medium. Nitrendipine showed high selectivity for the uterine smooth muscle because in a very high concentrations is exerted an insignificant relaxation of the other isolated smooth muscles (oesophagus, urinary bladder). Our experiments indicate that nitrendipine might have a role in therapy of premature delivery and abortion because of its great selectivity for the uterine smooth muscle. Addition of calcium into the medium restores completely all types of muscular activation after the inhibitory action of nitrendipine except its depressive action on the phasic component of oxytocin-induced contractions. These findings that individual types of activation, after inhibitory action of nitrendipine, are reestablished in various degrees by the addition of calcium into the medium, are also an additional confirmation about the existence of various types of calcium channels.

Acetylcholine↗
PubMed1984

Some recent pharmacological findings with nitrendipine.

The available evidence indicates that nitrendipine and other dihydropyridines with a similar pharmacological action exert their therapeutic effects by inhibiting Ca2+ channels. In our recent experiments, nitrendipine was shown to block K+-stimulated 45Ca2+ uptake and K+-induced contractions of isolated rabbit aortic rings. Its IC50 were 4.7 and 8.9 nM for inhibition of Ca2+ uptake and of contractions, respectively. There was no statistically significant difference between the two values. At higher concentrations, nitrendipine also reduced norepinephrine-induced 45Ca2+ uptake and norepinephrine-induced contractions of rabbit aortic strips. The norepinephrine-induced contractions were only slightly (21%) reduced by nitrendipine at 10 microM. Nitrendipine at 10 nM and higher concentrations inhibited K+- or angiotensin-II-(AII) induced release of aldosterone from isolated bovine adrenal glomerulosa cells. The drug was more potent and more effective in inhibiting K+- than AII-induced aldosterone release. Dantrolene, 25 microM, enhanced the inhibitory activity of nitrendipine on AII-stimulated aldosterone release. Acute renal failure produced by either glycerol or gentamicin in rats was antagonized by nitrendipine at oral doses of 15-25 mg/kg/day. Our studies confirmed previously reported observations that the usefulness of nitrendipine in the treatment of hypertension may be determined not only by its vasodilator action. We demonstrated that nitrendipine has a direct inhibitory effect on the release of aldosterone from adrenal glomerular cells. In addition to a previously described diuretic action, nitrendipine was shown to have renal cytoprotective activity.

Acute Kidney Injury↗
PubMed1984

The nitrendipine-sensitive Ca2+ channel in chick muscle cells and its appearance during myogenesis in vitro and in vivo.

The nitrendipine-sensitive Ca2+ channel of chick skeletal myotubes in culture has been studied using both the 45Ca2+ flux technique and [3H]nitrendipine binding experiments. Ca2+ uptake is insensitive to nitrendipine when chick myotubes in culture are polarized. Whereas depolarization reveals a new component of 45Ca2+ influx which is inhibited by nitrendipine. Half-maximal inhibition occurs at a nitrendipine concentration of 0.7 nM. This value is similar to the dissociation constant Kd = 0.4 nM found in [3H]nitrendipine binding experiments. During myogenesis in vitro the nitrendipine receptor is absent in myoblasts and appears in parallel with the fusion process. Two stages of increased binding have been observed in vivo. The first one, which occurs during embryonic life, has the same properties as in the in vitro development. The second stage occurs near hatching and corresponds to a large increase in the number of nitrendipine receptors. This increase is accompanied by a decrease of affinity of nitrendipine for its receptor by a factor of 4 to 10. Chronic denervation produces a further increase in the number of nitrendipine receptors which reaches a factor of about 2 at 15 days of denervation. Results are discussed in relation to the particular localization of these channels in transverse tubules and with the innervation.

Animals↗
PubMed1994

The dihydropyridine nitrendipine reduces N-methyl-D-aspartate (NMDA)-evoked currents of rodent cortical neurons through a direct interaction with the NMDA receptor-associated ion channel.

The 1,4-dihydropyridine (DHP) nitrendipine was previously shown to concentration-dependently (0.1-1 microM) reduce N-methyl-D-aspartate (NMDA)-evoked calcium influx and single-channel activity of mouse cerebellar granule cells and to reduce [3H]dizocilpine (MK-801) binding to mouse cortical and hippocampal membranes. Using patch-clamp electrophysiology, the present study was designed to understand further the specific mechanism of interaction between nitrendipine and NMDA receptors. Experiments were conducted with primary cultures of rodent cortical neurons and utilized whole-cell and excised outside-out patch configurations. NMDA-evoked whole-cell currents were reduced by nitrendipine (1 microM) in a voltage- and an agonist-dependent manner suggesting that nitrendipine interacts with NMDA receptors by a mechanism similar to that described for open channel blockers, such as extracellular magnesium and the dissociative anesthetics (e.g., MK-801). To examine this further, the effects of nitrendipine on NMDA-evoked single-channel activity were quantitated from outside-out patch recordings. In these studies, nitrendipine reduced the frequency of openings and bursts, reduced the average duration of openings and bursts and reduced the single open time constant for the main conductance (48 pS) in a concentration (0.03-1 microM)- and voltage-dependent manner. Because these effects of nitrendipine on NMDA-evoked currents were not readily reversible, the rate of nitrendipine dissociation is probably slower than the rate of NMDA-activated channel closing. Nitrendipine did not alter the main channel conductance at any concentration tested. Based on these results, a kinetic model of interaction between nitrendipine and NMDA receptors is proposed that is most similar to that previously described for MK-801.

Animals↗
PubMed1999

Efficacy and tolerability of moexipril and nitrendipine in postmenopausal women with hypertension. MADAM study group. Moexipril as Antihypertensive Drug After Menopause.

OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of the new angiotensin-converting enzyme (ACE) inhibitor moexipril and the calcium antagonist nitrendipine in postmenopausal women with mild to moderate hypertension. METHODS: After a 4-week placebo run-in period, 93 postmenopausal women (age range 44-70 years) with primary hypertension were randomized to receive moexipril 15 mg once daily or nitrendipine 20 mg once daily for 8 weeks. The mean sitting systolic (SSBP) and sitting diastolic blood pressures (SDBP) at baseline were 161.3/103.0 mmHg in the moexipril group, and 162.2/102.3 mmHg in the nitrendipine group. RESULTS: After the 8 weeks of treatment, the SSBP/SDBP reductions were -21.2/-15.2 mmHg in the moexipril group and -18.2/-13.6 mmHg in the nitrendipine group. Blood pressure responses were adequate in 82.2% of the moexipril-treated patients and in 80.9% in the nitrendipine-treated group. Adverse events were more frequent with nitrendipine than with moexipril. The most common adverse events in the nitrendipine group were headache (23.4%), flushing (21.3%) and ankle oedema (14.9%). In the moexipril group the most common adverse event was cough (8.9%). CONCLUSION: The results of the study suggest that moexipril and nitrendipine are equieffective in the given dosages. In the patient population of postmenopausal women, the ACE inhibitor moexipril appears to have an advantage over the calcium antagonist nitrendipine with regard to tolerability.

Aged↗
PubMed1986

Identification of two calcium channel receptor sites for [3H]nitrendipine in mammalian cardiac and smooth muscle membrane.

Various Ca-channel blockers differ in cardiovascular action despite common effects at the Ca channel. Many investigators have reported only a single high-affinity receptor for binding of [3H]nitrendipine, a dihydropyridine Ca-channel blocker. Its equilibrium dissociation constant (Kd) does not match the concentration of nitrendipine needed for a physiological effect on the mammalian cardiac Ca channel. The purpose of these studies was to clarify the existing discrepancy between pharmacological properties of nitrendipine receptors and the physiological effects of the dihydropyridine blockers. Of particular importance in this regard was to provide a pharmacological correlate for electrophysiological studies demonstrating multiple voltage-dependent conformational states of the Ca channel, which show differing affinities for the dihydropyridine Ca-channel blockers. By use of an improved ligand binding assay, our studies demonstrate both "high-affinity" and "low-affinity" [3H]nitrendipine receptors with Kd values corresponding well with observed physiologically effective nitrendipine concentrations. We detected two distinct populations of nitrendipine receptors in rat heart and bovine aortic membrane. A high-affinity Kd value of 0.2-0.3 nM was found, which seems to correspond to the physiologically functional state of the Ca channel in smooth muscle, since the Kd value is similar to the concentration at which nitrendipine inhibits contraction. However, in contrast to numerous other studies, we observed that the predominant component of [3H]nitrendipine binding (95-99%) had a low-affinity Kd value (235 nM). This putative low-affinity [3H]nitrendipine receptor may correspond to the physiologically functional state of the Ca channel in cardiac muscle.

Animals↗
PubMed1998

Effects of nitrendipine and enalapril on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension.

OBJECTIVE: To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension. DESIGN: A double-blind randomized, placebo-controlled trial. SETTING: General practitioners referred patients to the trial physician. PATIENTS: The study population comprised 121 patients with non-insulin-dependent diabetes mellitus. Inclusion criteria for blood pressure were diastolic blood pressure 90-115 mmHg and systolic blood pressure < or = 200 mmHg, while subjects were not being administered blood-pressure-lowering drugs for 3 weeks. INTERVENTION: Patients were randomly allocated to receive nitrendipine (n = 40), enalapril (n = 40) or placebo (n = 41). The treatment period was 48 weeks. MAIN OUTCOME MEASURES: The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment. The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly. Left ventricular mass was measured by M-mode echocardiography. RESULTS: Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures. During 48 weeks left ventricular mass index decreased by 5% for patients in the nitrendipine group (decrease by 12 g/m2, 95% confidence interval 1-23), remained about the same for patients in the enalapril group (decrease by 1 g/m2, 95% confidence interval decrease by 10 to increase by 9) and increased by 9% for patients in the placebo group (increase by 9 g/m2, 95% confidence interval 2-16). CONCLUSION: These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index. Enalapril appears not to induce regression, but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo.

Aged↗
PubMed1991

Effects of nitrendipine on sodium balance during changes in sodium intake and low-dosage ANP.

We found previously that calcium entry blockade with nitrendipine enhanced the natriuretic effect of high-dose atrial natriuretic peptide (ANP). It is unknown whether nitrendipine also influences the effect of physiological changes in ANP. We therefore studied the effect of nitrendipine on cumulative sodium balance during changes in sodium intake as well as on natriuresis after low-dosage ANP infusion during low and high sodium (LS and HS, respectively) intake. In eight healthy volunteers, sodium balance was recorded after the switch from LS (20 mmol/day) to HS (300 mmol/day) diet. Cumulative sodium balance was equal with (441 +/- 45 mmol) or without (458 +/- 45 mmol) nitrendipine treatment. The body weight curves were also fully congruent. ANP (0.005 micrograms/kg/min for 3 h) was administered during maximal water diuresis on both sodium intake levels with and without nitrendipine. Infusion of ANP increased sodium excretion (mumol/min) from 30 +/- 7 to 81 +/- 12 (LS) and from 316 +/- 27 to 469 +/- 46 (HS). During nitrendipine, similar increments (from 36 +/- 7 to 98 +/- 24 mumol/min, HS) were found. ANP had no effect on inulin clearance and fractional excretion of lithium, but consistently depressed diluting segment reabsorption. This pattern was also similar during nitrendipine. Apparently, under the conditions of this study in normal subjects, nitrendipine has no effect on sodium balance. ANP, in physiological concentrations, increases natriuresis mainly by depressing sodium reabsorption in the distal nephron, an effect not enhanced by nitrendipine.

Adult↗
PubMed1982

Binding of a calcium antagonist, [3H]nitrendipine, to high affinity sites in bovine aortic smooth muscle and canine cardiac membranes.

[(3)H]Nitrendipine, a potent calcium channel antagonist [3-ethyl-5-methyl-1-1,4-dihydro-2,6 - dimethyl - 4 - (3 - nitrophenyl) - 3,5 - pyridine carboxylate], was used to label high affinity binding sites on membranes prepared from bovine aortic smooth muscle. The binding of [(3)H]nitrendipine is rapid (t(1/2) < 5 min) and reversible at 37 degrees C. The binding sites have a high affinity for [(3)H]nitrendipine with an equilibrium dissociation constant of 2.1 nM. The density of sites is 40-60 fmol/mg of membrane protein. Analogues of nitrendipine compete for the binding sites with affinities consistent with their known biological effects as calcium antagonists. Nisoldipine, [isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine carboxylate], a calcium antagonist more potent than nifedipine [2,6-dimethyl-3,5-dicarbomethoxy-4-(2-nitrophenyl)-1,4-dihydropyridine] in relaxing vascular smooth muscle, has an affinity three-fold higher than that of nifedipine in competing for the binding sites. A biologically inactive derivative of nifedipine does not compete for [(3)H]nitrendipine binding. Verapamil (alpha-isopropyl-alpha[(N-methyl - N-homoveratryl) -alpha-aminopropyl]-3,4-dimethyoxyphenyl acetonitrile), a structurally different calcium antagonist, only partially (25%) inhibits binding at high concentrations (1 muM). Prazosin, an alpha adrenergic antagonist does not compete for [(3)H]nitrendipine binding sites. The binding of [(3)H]nitrendipine is not affected by 1.5 mM calcium. Canine cardiac membranes also have high affinity [(3)H]nitrendipine binding sites, (K(D) = 6 nM) but bovine erythrocytes do not. The relative affinities of nisoldipine and nifedipine for the cardiac membrane binding sites reflect the relative activities of these compounds as calcium channel antagonists. These results suggest that the [(3)H]nitrendipine binding sites are the sites through which dihydropyridines act as calcium channel antagonists.

Animals↗
PubMed1988

Nicardipine, nitrendipine, and bepridil: new calcium antagonists for cardiovascular disorders.

The chemistry, pharmacology, pharmacokinetics, clinical uses, and adverse effects of nicardipine, nitrendipine, and bepridil are reviewed. Nicardipine, nitrendipine, and bepridil are calcium antagonists under investigation for the treatment of cardiovascular disorders. Nicardipine and nitrendipine share a common dihydropyridine nucleus with the calcium antagonist nifedipine; bepridil is unrelated to other known calcium antagonists. Like nifedipine, nicardipine and nitrendipine produce peripheral vasodilation as their predominant in vivo effect. Bepridil has vascular, sinoatrial and atrioventricular nodal, and myocardial effects qualitatively similar to those of the calcium antagonist verapamil; it also interferes with the fast sodium channel and prolongs refractoriness in atrial and ventricular tissue. Nicardipine and nitrendipine undergo extensive first-pass hepatic extraction after oral administration; oral bioavailability of bepridil is about 60%. All three drugs are highly protein bound and have been reported to increase plasma digoxin concentrations. Both nicardipine and nitrendipine are effective antihypertensive agents used alone or combined with diuretics, beta blockers, or angiotensin-converting enzyme inhibitors. Nicardipine and bepridil effectively control angina, and preliminary studies indicate that nitrendipine has antianginal properties. Bepridil may be useful in the treatment of various cardiac arrhythmias; however, its tendency to cause or worsen cardiac arrhythmias and its association with torsade de pointes may limit its usefulness. Nicardipine and nitrendipine have similar adverse effect profiles, with vasodilation-related complaints being most common. Since nicardipine, nitrendipine, and nifedipine are similar in efficacy and safety, the eventual availability of sustained-release dosage forms may determine how these drugs are ultimately used. Bepridil is an effective antianginal drug, but, because of its proarrhythmic potential, it should probably not be used as a first-line agent.

Bepridil↗