Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nisoldipine is a calcium antagonist that specifically blocks the slow or voltage-dependent calcium channel up to the highest concentrations. This mode of action has been confirmed in pharmacological studies on isolated organs, electrophysiological and binding studies, and by the measurement of transmembrane calcium transport. As with other dihydropyridine calcium antagonists, an interaction with intracellular calcium reservoirs and calmodulin seems to be of minor importance. The drug exhibits higher potency, longer duration of action, and a higher binding affinity in vitro and in vivo than nifedipine. In contrast to its vasodilating and spasmolytic activity, its negative inotropic effect occurs in vitro only after higher concentrations than after nifedipine. In whole animals a secondary positive inotropic effect occurs regularly owing to sympathetic counter-regulation. The influence of nisoldipine on cardiac stimulus formation and conduction is also very slight in anesthetized animals, and is completely eliminated in awake animals and humans by counter-regulation up to very high doses. The cardiac anti-ischemic action of nisoldipine has been demonstrated in various ischemia models and is probably based predominantly on its afterload-reducing properties in addition to its spasmolytic effect on the coronary arteries. Various other suspected effects, for which there are isolated indications, e.g., inhibition of thromboxane synthesis, preload reduction, interaction with the transport of adenosine, and normalization of the sarcolemmal Na+, K(+)-ATPase activity, are probably of subordinate importance. Its antihypertensive effect is explained primarily by lowering of the peripheral resistance. There are, however, some indications that nisoldipine exerts certain effects over and above pure vasodilation. The prevention of postischemic calcium overloading in the renal tubule epithelium and the natriuretic effect are probably of importance in the therapeutic action. Clinically, nisoldipine was found more potent and prolonged in its action in comparison with nifedipine. In comparative studies, nisoldipine, 10 mg once a day, was found equieffective with nifedipine 10 mg three times or 20 mg twice a day in angina or hypertension, respectively.
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PMID:The pharmacology of nisoldipine. 315 74

Recent clinical reports have suggested that hypertension accelerates the progress of diabetic nephropathy and retinopathy, whereas antihypertensive treatments may retard them. Thus, the effect of antihypertensive treatment in diabetes mellitus with hypertension was evaluated in rats. A model of diabetes mellitus with hypertension has been developed in spontaneously hypertensive (SHR) rats by unilateral nephrectomy and streptozotocin (STZ, 30 mg/kg, i.v. treatment). The rats were treated with four antihypertensive drugs orally for 12 weeks thereafter. STZ treatment induced chronic hypeglycaemia (300-400 mg/dl), decreased body weight and heart rate, and caused vascular changes of ophthalmic fundi and cataracta. The kidney of these rats showed proliferative changes such as periarteritis nodosa, hyperplasia, or fibronecrosis of the arterioles, exudative changes, mesangial proliferation, or thickening of the basement membrane of the glomeruli. Enalapril (10 mg/kg per day) and remipril (Hoe 498) (1 mg/kg per day), converting enzyme inhibitors, or arotinolol (20 mg/kg per day), a beta-adrenoceptor blocking drug, decreased blood pressure, prevented the development of renal and ocular lesions, and tended to increase creatinine clearance. Nisoldipine (3 mg/kg per day), a calcium-entry blocking drug, tended to decrease blood glucose, and prevented the decrease of body weight and development of ocular lesions. In conclusion, antihypertensive treatments were effective in preventing the progress of diabetic retinopathy and nephropathy, and renal insufficiency in this animal model.
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PMID:Antihypertensive treatment in spontaneously hypertensive rats with streptozotocin-induced diabetes mellitus. 329 54

The effects of CV-4093, a new dihydropyridine derivative, on isolated cardiovascular tissues were compared with those of several dihydropyridine and non-dihydropyridine calcium antagonists. CV-4093 effectively inhibited the contractions induced in canine femoral arteries by high [K+]0 and Bay K 8644, but incompletely relaxed those induced by norepinephrine. CV-4093, 10(-6) M, abolished the electrically induced slow action potentials in guinea-pig papillary muscles partially depolarized by 25 mM K+ solution and attenuated those induced by isoproterenol, histamine and Bay K 8644. The rank order of potency of dihydropyridine and non-dihydropyridine calcium antagonists in canine femoral arteries and veins precontracted with 120 mM [K+]0 was as follows: nisoldipine greater than nicardipine greater than or equal to nifedipine greater than or equal to CV-4093 greater than verapamil greater than or equal to diltiazem. Nisoldipine was the most potent and CV-4093 was the least potent among these drugs in terms of negative inotropic effect in normally polarized papillary muscles and negative chronotropic effect in right atria of guinea pigs. The rank order of potency for these cardiodepressant actions was nisoldipine greater than or equal to nifedipine greater than nicardipine greater than verapamil greater than diltiazem greater than or equal to CV-4093. The duration of action potential in guinea-pig papillary muscles was shortened by nisoldipine and nifedipine, unchanged by nicardipine and CV-4093 and was slightly prolonged by verapamil and diltiazem. These results suggest that CV-4093 is a calcium antagonist with a highly selective vascular effect and little cardiodepressant action, and could be of value for the treatment of hypertension.
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PMID:Cardiac versus vascular effects of a new dihydropyridine derivative, CV-4093. In vitro comparison with other calcium antagonists. 335 58

The use of nisoldipine (10-20 mg b.i.d.) was evaluated as a replacement therapy for long-acting nifedipine (40-120 mg/day) in 21 patients with severe hypertension, who were resistant to or intolerant of nifedipine. Except for one patient with specific contraindications, all participants received an individually determined constant dose of beta blocker throughout the 8-month study. Results indicated a significant decrease in blood pressure after four weeks of treatment with nisoldipine (173 +/- 5/98 +/- 4 to 156 +/- 3/91 +/- 2 mmHg, p less than 0.05) without an associated change in pulse rate in 19 patients; only 5 of the 21 patients showed no further benefit from nisoldipine. No significant biochemical changes were noted in any of the patients during the study. In three patients, leg edema that had developed as a consequence of previous nifedipine therapy resolved completely following nisoldipine administration. Two patients withdrew from the study before term because of headaches and palpitations. An additional two patients suffered headaches, but tolerated the drug and continued the study. One patient suffered from polyuria. Nisoldipine appears to be an effective substitute treatment for nifedipine in severely hypertensive patients sensitive or resistant to nifedipine.
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PMID:Nisoldipine: a replacement therapy for nifedipine in the treatment of severe hypertension. 338 70

The effect of nisoldipine, a new calcium antagonist, on rats with renovascular hypertension was evaluated. Eight one-kidney, one clip hypertensive rats (1K, 1C rats) given nisoldipine 10 mg/kg for 4 weeks were compared with eight 1K, 1C hypertensive control rats. Fifteen other rats underwent sham-operation (right nephrectomy, no clip), of which eight received nisoldipine in the same dosage. A significant decrease in systolic blood pressure (BP) was achieved in the nisoldipine groups: from 154 +/- 4 to 107 +/- 7.5 mmHg in the 1K, 1C group (P less than 0.005) and from 117 +/- 4.2 to 89 +/- 5.4 mmHg in the sham-operated rats (P less than 0.01). The significant decrease in BP was maintained for only 6 days, but did not rise markedly throughout the entire study. Four 1K, 1C control rats died before term, two after 14 days and two after 20 days. There was no significant change in the pulse rate. Sugar and cholesterol levels in the nisoldipine groups remained constant. Nisoldipine caused a natriuresis without kaluresis in both groups: sodium excretion in the 1K, 1C rats increased from 0.25 +/- 0.05 to 2.32 +/- 0.2 mmol/day, and from 0.34 +/- 0.1 to 1.85 +/- 0.15 mmol/day in the sham-operated rats. A slight decrease in aldosterone levels in the 1K, 1C rats was observed. It appears that the combination of both natriuretic and vasodilatory effects during nisoldipine treatment results in a favourable hypotensive response in 1K, 1C hypertensive rats.
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PMID:The hypotensive effect of nisoldipine in renovascular hypertensive rats. 347 95

The acute antihypertensive effects and pharmacokinetics of orally administered nisoldipine (Bay k 5552) were compared with those of nifedipine, nimodipine and nicardipine in conscious renal hypertensive dogs. The antihypertensive effects of hydralazine were also investigated. Nisoldipine as well as nifedipine, nimodipine and nicardipine dose-dependently lowered mean blood pressure, which was significant 0.5 h and reached its peak effect 1 to 2 h after dosing. Significant antihypertensive effects of hydralazine started 1 h and peaked 3 h after dosing. Of the drugs used, nisoldipine showed the most potent and the longest antihypertensive effects. The fall in mean blood pressure by the drugs was accompanied by a significant increase in heart rate. The tachycardia by nisoldipine and nimodipine, but not by nifedipine and nicardipine, was not dose-dependent. The tachycardia by nisoldipine was not significantly different from those by the other four drugs. The plasma nisoldipine concentration was significantly correlated with the fall in mean blood pressure. This was also the case for nifedipine, nimodipine or nicardipine. However, the slope of the regression line for nisoldipine obtained by plotting the antihypertensive effects against plasma concentrations was greater than those for the other 1,4-dihydropyridines examined. Nisoldipine had the lowest maximum plasma concentration and the longest elimination half-life among the four 1,4-dihydropyridines, resulting in no significant difference in the area under the plasma concentration-time curve. These results suggest that of the drugs examined, nisoldipine is the most potent, has the longest duration of action making it useful for long-term treatment of hypertension.
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PMID:Comparative study on acute antihypertensive effects and pharmacokinetics of nisoldipine, nifedipine, nimodipine and nicardipine administered orally to conscious renal hypertensive dogs. 381 8

The effects of nisoldipine administration on vascular reactivity to humoral and neural vasoconstrictor stimuli were examined in the intact rat. For these experiments, rats were instrumented with miniaturized pulsed Doppler flow probes to allow continuous measurement of renal, mesenteric, and hindquarters blood flow. In conscious and anesthetized rats, intravenous doses of angiotensin II (75 and 150 ng/kg), norepinephrine (0.6 and 1.2 microgram/kg), and epinephrine (0.6 and 1.2 microgram/kg) caused dose-dependent increases in arterial pressure and renal and mesenteric vascular resistance. Nisoldipine (0.7 microgram/min) administration significantly attenuated (p less than 0.05) the pressor and regional vasoconstrictor actions of all three circulating pressor agents; however, nisoldipine infusion had little effect on neurally mediated regional vasoconstrictor responses elicited by electrical stimulation of the posterior hypothalamus or greater splanchnic nerve. These data indicate that nisoldipine depressed vascular responsiveness to humoral vasoconstrictor agents, while neural vasoconstrictor responses were unaffected. Thus nisoldipine appears to exert preferential antagonistic effects on humoral rather than on neural vasoconstrictor stimuli.
Hypertension
PMID:Selective antagonism of humoral versus neural vasoconstrictor responses by nisoldipine. 398 68

This article examines trials of the use of two types of drugs in the treatment of myocardial infarction: angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists. ACE inhibitors are an established treatment for hypertension and heart failure and have been shown to reduce mortality from heart failure and after myocardial infarction. Six large studies have been carried out. In 1 in which an ACE inhibitor was given 3-16 days after infarction in patients with an ejection fraction < 40%, mortality was reduced by 17%. In a second study of patients who had evidence of heart failure and were followed up for 15 months, treatment with ACE inhibitors was given 3-10 days after myocardial infarction and mortality was reduced by 27%. Two other studies of 11,000 and 50,000 unselected patients with myocardial infarction showed only marginal clinical benefit. Calcium antagonists were introduced to treat hypertension and angina pectoris. In trials with patients with heart failure, the results have not been encouraging, and in some patients these agents seem to be harmful. Recently, long-acting calcium antagonists have become available, and these may avoid the deleterious effects of short-acting drugs. Since calcium antagonists act on smooth muscle, they may increase myocardial blood flow to improve function after "stunning" or "hibernation." This idea was investigated with a long-acting dihydroyridine calcium, antagonist in a randomized double-blind, placebo-controlled study (Doppler Flow, Echocardiography, and Functional Improvement Assessment of Nisoldipine Therapy-I--DEFIANT I), and a further study is being carried out. At present the widespread use of calcium antagonists after infarction is not recommended.
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PMID:Angiotensin-converting enzyme inhibitors and calcium antagonists after acute myocardial infarction. 772 23

Nisoldipine is a second-generation dihydropyridine calcium antagonist structurally related to nifedipine and used in the treatment of stable angina and arterial hypertension. It is also under investigation for the treatment of left ventricular dysfunction. It was first developed as an immediate release tablet, but this formulation was not considered optimal for once-daily administration because of the variable results obtained at peak and trough in clinical studies. Consequently, nisoldipine coat core (CC) was developed with the aim of optimizing the drug's time--effect profile over the 24-hour dosing interval. The in vitro release pattern classifies this tablet as an "extended release" formulation according to European Community guidelines. The present article outlines the pharmacokinetic and pharmacodynamic profiles of nisoldipine CC, as obtained from recent clinical studies.
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PMID:Clinical pharmacology of nisoldipine coat core. 772 24

The effects of the long-acting dihydropyridine calcium antagonist nisoldipine coat core (CC) have been investigated in > 3,500 patients with angina pectoris, hypertension, and ischemic ventricular dysfunction. In patients with angina pectoris, nisoldipine CC improved total treadmill exercise duration (p = 0.027), delayed the onset of angina pectoris (p = 0.009), and increased time to exercise-induced ST-segment depression (p = 0.061). In general, nisoldipine 20-40 mg was effective, and the dose-response curve flattened thereafter. In patients with hypertension, 10-40 mg once daily as monotherapy reduced blood pressure (p < 0.05), with a fall in diastolic pressure of > or = 10 mm Hg or a final diastolic pressure of < 90 mm Hg in 35-63% of patients. In most patients followed for a year, nisoldipine CC was continued as monotherapy. Efficacy was similar in patients < 65 and > 65 years of age. In the Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy (DEFIANT-I) study of patients recovering from myocardial infarction, nisoldipine CC had a salutary effect on diastolic ventricular function, with a higher transmitral early filling velocity and shorter isovolumic relaxation time than in patients receiving placebo. Bicycle exercise capacity was greater (by 12 W; 95% confidence interval, 0.8-23.3) and exercise-induced ischemia occurred less frequently. The nisoldipine CC data pool (3,679 patients) showed that the drug was well tolerated with a low incidence of side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy and safety of nisoldipine coat core in the management of angina pectoris, systemic hypertension, and ischemic ventricular dysfunction. 772 25


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