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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the inhibitory effects of nifedipine, a calcium channel blocker, on airway smooth muscle constriction in the guinea pig. In vitro, nifedipine (0.003 to 3.0 microM) caused significant dose-dependent reversal of intrinsically existing tone in both tracheal spirals and parenchymal strips. Nifedipine also inhibited the constriction of tracheal spirals and parenchymal strips induced by two different agonists, histamine and carbachol. At a concentration of 3.0 microM, nifedipine increased by 48-fold the concentration of carbachol required to produce a 50% of maximal contraction of parenchymal strips, and by 5-fold the concentration of histamine. Increasing extracellular calcium ion concentration in the tissue baths significantly diminished the inhibitory action of nifedipine. In vivo, nifedipine (30 micrograms/kg body weight given intravenously) did not alter pulmonary resistance or dynamic compliance. It did, however, attenuate histamine-induced bronchoconstriction in 3 of 5 animals studied. In response to the maximal dose of histamine infused, mean pulmonary resistance rose 40 +/- 16% (SEM) after nifedipine versus 182 +/- 65% in the control animals (p less than 0.025) and mean dynamic compliance decreased 35 +/- 8% after nifedipine versus 58 +/- 6% in the control animals (p less than 0.01). Thus, this calcium channel blocker inhibits mediator-induced constriction of both central and peripheral airway contractile tissues, a finding of potential clinical applicability.
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PMID:Inhibition of bronchoconstriction in the guinea pig by a calcium channel blocker, nifedipine. 706 12

A new calcium channel blocker, niludipine, was administered intravenously to nine patients with coronary artery disease in order to investigate its effects on left ventricular systolic and diastolic function, coronary sinus blood flow, and myocardial lactate metabolism. Coronary sinus pacing was performed in all patients and produced angina in six patients. Niludipine increased the resting heart rate from 75+/-3 beats/min (mean+/-SEM) to 82+/-3 (NS) and decreased the left ventricular systolic pressure from 155+/-4.7 mm Hg to 134+/-2.8 (p less than 0.05). Coronary sinus blood flow increased by 9%(NS). During pacing after niludipine, clinical improvement occurred in the six patients who had initially experienced angina. The extent of ischemic ST segment depression was decreased (-1.56+/-0.27 mm to -0.78+/-0.38, p less than 0.02) and myocardial lactate metabolism was improved. When pacing was terminated, niludipine suppressed the elevation of left ventricular end-diastolic pressure compared to pretreatment values (16.2+/-2.5 mm Hg vs 8.5+/-0.9, p less than 0.05) and decreased the left ventricular time constant T(26.4+/-3.6 msec to 20.2+/-2.4 p less than 0.05). The results suggest that niludipine appears to be beneficial in reducing systolic and diastolic work of the left ventricle during pacing induced angina without a significant change in total coronary sinus blood flow. Niludipine appears to have less of a hypotensive and reflex tachycardic effect than nifedipine.
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PMID:Effects of new calcium channel blocker of niludipine on the coronary hemodynamics, diastolic properties, and metabolic responses to tachycardia stress in patients with coronary disease. 712 62

We examined the antiproliferative effect of the novel multiple-action antihypertensive agent carvedilol on human vascular smooth muscle cells (VSMC). Carvedilol inhibited the increase in cell number induced by foetal calf serum (FCS) in 86% (18 of 21) of human VSMC grown both from saphenous vein (17.6 +/- 3.5% inhibition, mean +/- SEM, n = 15) and restenotic lesions (31.4 +/- 5.5% inhibition, mean +/- SEM, n = 5). Carvedilol had a greater antiproliferative effect than other beta-adrenoceptor antagonists. In comparison with calcium channel blockers, carvedilol (10 microM) elicited a degree of growth inhibition similar to that of verapamil, but was less effective than the dihydropyridine amlodipine at equimolar concentrations. Although carvedilol had a greater antiproliferative effect on cells derived from restenotic lesions cells than on control saphenous vein cells, the difference was not statistically significant. In the present study, the antiproliferative effect of carvedilol on human VSMC in vitro occurred at concentrations higher than those in plasma. Although this may represent a limitation to the clinical efficacy of carvedilol against proliferation of VSMC associated with hypertension and atherosclerosis, the apparent relative selectivity of carvedilol for restenosis-derived cells is a promising line of investigation.
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PMID:Inhibition of human vascular smooth muscle cell proliferation by the novel multiple-action antihypertensive agent carvedilol. 759 35

The effects of the intravenous administration of a calcium channel blocker, verapamil (0.0833 mg/min for 2-3 h after a 5 mg bolus) on prolactin (PRL) and thyrotropin (TSH) circulating levels were assessed in 7 normal subjects and in 17 patients with hyperprolactinemia (11 with prolactinoma and 6 sulpriride-induced). In the normal group a non-significant increase in PRL levels occurred (mean +/- SEM = 11.7 +/- 2.9 micrograms/l verapamil vs. 8.5 +/- 1.4 micrograms/l saline). In this control group the peak response of PRL and TSH to TRH (thyrotrophin releasing hormone) during verapamil or saline was also determined: PRL = 112.0 +/- 27.0 micrograms/l on verapamil vs. 53.6 micrograms/l on saline, p = 0.02; TSH 7.1 +/- 0.7 microU/l on verapamil vs. 9.0 +/- 0.6 mU/l on saline, p = 0.01. In the hyperprolactinemic subjects verapamil induced opposite effects on PRL levels, the prolactinoma group exhibiting an increase in the mean values (168.5 +/- 22.3 micrograms/l vs. 150.8 +/- 23.6 micrograms/l on saline, p = 0.04) whereas in the sulpiride-induced there was a reduction in the mean PRL levels (61.1 +/- 13.8 micrograms/l vs. 78.5 +/- 19.3 micrograms/l on saline, p = 0.002). In both groups of hyperprolactinemic patients no effects on TSH levels were observed. The authors discuss the possibility that the divergent effects of verapamil in hyperprolactinemia of different etiologies could be related to the balance between dopamine and calcium channel effects on hypothalamus and/or pituitary.
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PMID:Calcium and prolactin secretion in humans: effects of the channel blocker, verapamil, in the spontaneous and drug-induced hyperprolactinemia. 785 73

The effects of withdrawal from long-term administration of nifedipine (2.5 mg/kg, ip, twice daily for 30 days) on open-field habituation were evaluated in 3-month old male Wistar rats (13-14 animals per group). Habituation was evaluated by the ratio between locomotion or rearing frequencies obtained in the second and the first open-field session for each animal. Nifedipine treatment did not modify the locomotion ratio (with a mean +/- SEM ratio of 0.66 +/- 0.12 for control and 0.45 +/- 0.08 for nifedipine-treated group) nor the rearing ratio (with a mean +/- SEM ratio of 0.51 +/- 0.12 for control and 0.62 +/- 0.18 for nifedipine-treated group). The possible factors underlying the discrepancy between the present results and the commonly reported positive effects of calcium channel blockers on memory are discussed.
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PMID:Effect of withdrawal from long-term nifedipine administration on open-field habituation in the rat. 789 49

The aim of the present study was to investigate the renal effects of long-term treatment with the calcium channel blocker nifedipine in normotensive type 1 diabetic patients with microalbuminuria. In a randomized, double-blind trial, 15 type 1 diabetic patients were treated with either nifedipine (n = 8; dosage 30 mg/day) or placebo (n = 7) for 12 months. At baseline and after 6 and 12 months of therapy, the albumin excretion rate (UAER, radioimmunoassay), glomerular filtration rate (GFR, chromium 51 ethylenediamine tetra-acetic acid clearance) and renal plasma flow (RPF, iodine 125 hippuran clearance) were determined. Nifedipine treatment caused a significant reduction of UAER after 6 and 12 months (median, Q1/Q3 in mg/24 h): baseline 84 (65/163); 6 months 35 (23/90), P < 0.02; 12 months 39 (15/79), P < 0.05). GFR was significantly decreased by nifedipine treatment (baseline 157 +/- 15, 6 months 122 +/- 8, 12 months 111 +/- 47 ml/min; P < 0.05, mean +/- SEM), whereas RPF remained constant. Nifedipine treatment did not influence systolic (baseline 121 +/- 7, 12 months 124 +/- 2 mmHg, mean +/- SEM) or diastolic (baseline 72 +/- 2, 12 months 74 +/- 3 mmHg) arterial blood pressure. With placebo treatment no significant alterations of UAER, GFR, RPF and arterial blood pressure were observed. Metabolic control was constant throughout the whole study period. Thus, 1 year's treatment with nifedipine reduces the UAER and GFR in normotensive type 1 diabetic patients without influencing the systemic arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term treatment with nifedipine reduces urinary albumin excretion and glomerular filtration rate in normotensive type 1 diabetic patients with microalbuminuria. 804 91

The effects of single (2.5 and 5.0 mg/kg) and long-term (2.5 mg/kg, twice daily, for 30 days) ip administration of nifedipine on open-field and apomorphine-induced stereotyped behavior were evaluated in young male Wistar rats (12-16 animals per group for the open-field studies and 7 animals per group for the stereotypy experiments). Administration of a single dose of nifedipine produced no changes in ambulation or rearing frequencies or in immobility duration in the open-field compared to controls. Similarly, treatment with a single dose of nifedipine did not modify apomorphine-induced stereotypy. Withdrawal from long-term nifedipine administration caused a significant increase only in rearing frequency 24 h after the last drug injection (with a mean +/- SEM frequency of 23.2 +/- 2.8 for the nifedipine group and of 14.7 +/- 2.0 for control rats, after 6-min observation). This enhancement of rearing frequency was no longer observed 48 h after abrupt nifedipine withdrawal (means +/- SEM: 15.0 +/- 2.2 and 19.6 +/- 2.7 for nifedipine-treated and control rats, respectively). The other open-field behavioral parameters and apomorphine-induced stereotypy (which was observed 96 h after nifedipine withdrawal) were not affected by long-term nifedipine treatment; for example, the sum of stereotypy scores (mean +/- SEM) was 26.9 +/- 3.0 for nifedipine-treated rats and 25.5 +/- 2.2 for vehicle-treated animals. The possible mechanisms underlying these results are discussed in light of the changes in dopaminergic neurotransmission induced by dihydropyridine calcium channel blockers.
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PMID:Effects of single and long-term administration of nifedipine on dopamine-related behaviors. 808 Dec 97

Steady-state fluorescence anisotropy measurements of the fluorescent hydrocarbon probe 1,6-diphenyl-1,3,4-hexatriene (DPH) were carried out in isolated hepatocytes of saline control and Salmonella enteritidis endotoxin (20 mg/kg) injected rats. Statistically significant differences were observed in the fluorescent anisotropy (rs) and membrane microviscosity (eta) values of control (rs = 0.107 +/- 0.004 (SEM), eta = 0.98 +/- 0.08, n +/- 6) versus endotoxin injected rat hepatocytes (rs = 0.134 +/- 0.005, eta = 1.43 +/- 0.08, n = 6, p < 0.001) at 37 degrees C. Fluidity was similarly lower in the isolated plasma membrane preparations from endotoxin-injected rat livers relative to control livers. When endotoxin-injected rats were treated with the calcium channel-blocker diltiazem, the anisotropy and microviscosity values were comparable to those obtained from control rats (rs = 0.152 +/- 0.003, eta = 1.00 +/- 0.003, n = 6). These measurements were made in animals five hours after endotoxin had been injected, and thus represent the in vivo effects of bacterial endotoxins. Temperature scan studies of DPH from 5-40 degrees C revealed that the membrane fluidity of endotoxin-injected rat hepatocytes was significantly lower than control hepatocytes at all temperatures investigated. The data suggest that endotoxin alters the membrane fluidity of hepatocytes, and that calcium-channel blockers can prevent the alteration. Our previous studies have shown that calcium channel blocker prevented endotoxin induced alterations in hepatic cellular regulation of Ca2+. Thus, cellular calcium homeostasis may be important in the maintenance of membrane fluidity and other membrane-associated transport functions.
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PMID:Altered membrane fluidity in rat hepatocytes during endotoxic shock. 831 31

The efficacy of diltiazem, a calcium channel blocker, for reducing the dose requirement for nitroprusside-induced hypotension was studied in 20 healthy patients during spine fusion for scoliosis. Anesthesia included methohexital (3 mg/kg followed by 3 mg.kg-1.h-1 intravenously), nitrous oxide, and alfentanil (40 micrograms/kg, followed by 0.7 microgram.kg-1.min-1 intravenously). Patients were assigned randomly to two groups, receiving either nitroprusside alone or nitroprusside and diltiazem (bolus of 80 micrograms/kg with two consecutive infusions of 4.5 micrograms.kg-1.min-1 during the first 30 min and then 1.3 micrograms.kg-1.min-1). Nitroprusside was used to maintain mean arterial pressure at 55-60 mm Hg in both groups. Hypotension was obtained in similar times, 4 min in the group receiving nitroprusside alone (range, 1-8 min) and 2 min in the group receiving nitroprusside and diltiazem (range, 1-8 min). Nitroprusside administration lasted 186 +/- 17 min (mean +/- SEM) in the group receiving nitroprusside alone and 214 +/- 26 min (mean +/- SEM) in the other group (NS). After hypotension, arterial blood pressure returned to its initial value in a time of 7 min in the group receiving nitroprusside alone (range, 5-9 min) and 9 min in the group receiving nitroprusside and diltiazem (range, 7-13 min) (NS). Cumulative doses of nitroprusside were larger in the group receiving nitroprusside alone (0.47 +/- 0.07 mg/kg; mean +/- SEM) than in the other group (0.24 +/- 0.05 mg/kg; mean +/- SEM) (P < 0.01). Significant increase in plasma thiocyanate concentration, cardiac index, and heart rate was observed only in the group receiving nitroprusside alone, but no intergroup differences were found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diltiazem reduces the dose requirement for nitroprusside-induced hypotension. 834 32

Physical forces such as fetal breathing and fluid secretion may influence lung development, perhaps by their ability to distend the fetal lung. We found that airway smooth muscle cells in first-trimester human lung tissue and cultured lung tissue explants spontaneously contract. The contractions caused visible movement of intraluminal fluid and distended the distal ends of the epithelial tubules, suggesting that they produced significant changes in intraluminal pressure. Smooth muscle contractility and responses to pharmacologic manipulations were recorded with video microscopy. The interval between contractions ranged from 8 to 135 s (mean +/- SEM, 54 +/- 5 s; n = 20). Smooth muscle contractility was not inhibited by tetrodotoxin or atropine, implying a myogenic rather than neurogenic origin. Because cholinergic nerves modulate adult airway smooth muscle contractility, we asked whether fetal airway smooth muscle cells were regulated by cholinergic agents. The cholinergic agonists acetylcholine and carbachol both increased fetal airway smooth muscle contractility. Contractions were inhibited by the calcium channel blockers CdCl2 and nifedipine, suggesting that an influx of extracellular Ca2+ accompanied airway smooth muscle contractions. Isoproterenol dilated the contractile regions of the epithelial tubules and stopped contractions. Lemakalim, an activator of smooth muscle ATP-sensitive K+ channels, also arrested contractions and relaxed fetal airway smooth muscle. In conclusion, human fetal airway smooth muscle contacts spontaneously and exhibits pharmacologic responsiveness similar to adult airway smooth muscle. We speculate that fetal airway smooth muscle contractions, possibly exerting effects through phasic changes in intraluminal pressure, may be an important physical force contributing to lung development.
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PMID:Spontaneous contractility of human fetal airway smooth muscle. 848 Dec 38


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