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

The central nervous system modulates cardiovascular function and fluid and electrolyte balance in part through the actions of vasoactive peptides/neurotransmitters. The presence of several vasoactive peptides and their receptors in the hypothalamus suggests a possible interaction at this site. One level at which vasoactive peptides such as arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) might interact is through the mutual regulation of production and secretion in the hypothalamus. To determine whether AVP modulates ANP gene expression and secretion, we cultured fetal rat diencephalic neurons in the presence of AVP. AVP induced a significant increase in ANP secretion in dose-related fashion (mean +/- SEM basal ANP, 87 +/- 4 pg/ml; maximal mean AVP-stimulated ANP, 146 +/- 6 pg/ml; P less than 0.05, by analysis of variance). Neither oxytocin nor the vasoactive neuropeptide angiotensin-II had any effect on ANP secretion. The stimulatory effect of AVP was significantly blocked by coincubation with a V1 receptor antagonist, but was unaffected by a V2 receptor antagonist. The immunoreactive ANP secreted in response to AVP was the major brain isoform, ANP-(103-126). Coincubation with a calcium channel antagonist, nifedipine, had no effect on AVP-induced ANP secretion, while ryanodine, an inhibitor of intracellular calcium mobilization, significantly reduced the stimulatory effect of AVP. AVP induced a dose-related, nearly 3-fold maximal increase in ANP mRNA expression at 4 h. Coincubation of the neurons with a V1 receptor antagonist also significantly attenuated the increased ANP gene expression induced by AVP. These results indicate that AVP acts directly through V1 receptors on cultured fetal rat diencephalic neurons to augment ANP gene expression and secretion of the peptide. The effects are probably related to AVP-stimulated mobilization of intracellular calcium and not the result of calcium influx into the cell. These studies provide the first evidence that AVP modulates ANP production from cultured neurons. In the central nervous system, these two vasoactive neuropeptides might interact in part through the regulation of ANP production by AVP.
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PMID:Arginine vasopressin stimulates atrial natriuretic peptide gene expression and secretion from rat diencephalic neurons. 138 Apr 42

Clentiazem, 8-chloro diltiazem, is a calcium channel blocker currently undergoing evaluation for the treatment of stable angina and hypertension. As patients with ischaemic disorders often present some degree of heart failure, the aim of this study was to investigate the effect of congestive heart failure on clentiazem (200 micrograms kg-1, i.v. bolus) pharmacokinetics in a canine model. Congestive heart failure was induced in six dogs by rapid ventricular pacing (240 beats min-1) for 3-5 weeks. Clentiazem pharmacokinetics was studied in each dog under the control condition and after the development of clinical signs of heart failure (ascites, dyspnea, fatigue). Blood samples were collected up to 480 min post-dose. Clentiazem plasma concentrations were determined by high performance liquid chromatography. The area under the plasma concentration versus time curves (AUC0-infinity) was significantly increased in congestive heart failure dogs (8.8 +/- 1.6 vs 21.8 +/- 1.4 micrograms min ml-1) (mean +/- SEM). These changes were related to a reduction of the volume of distribution of the central compartment (0.9 +/- 0.1 vs 0.2 +/- 0.11 kg-1) and total body clearance (1.9 +/- 0.4 vs 0.7 +/- 0.21 h-1 kg-1). It is concluded that, in our model, congestive heart failure significantly modifies clentiazem disposition. These results suggest that caution should be exercised when clentiazem is given to patients with a low ejection fraction and a compromised cardiac function. Reduced loading and maintenance doses might be recommended in patients with severe congestive heart failure.
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PMID:Effect of congestive heart failure on clentiazem pharmacokinetics in a dog model. 148 42

Glomerular hyperfiltration and hypertension induced by extensive loss of renal parenchyma are suspected to accelerate progression of renal failure. Amino acid infusion or protein ingestion also modify renal hemodynamics and increase glomerular filtration rate (GFR). This phenomenon was used to study the influence of two commonly used antihypertensive agents, captopril and nifedipine, on renal hemodynamics at rest and during glomerular hyperfiltration. Thirteen healthy volunteers were studied on three separate days (days A, B, and C) in random sequence: inulin and p-amino hippurate (PAH) clearance were measured first under glucose infusion and afterwards under stimulation by amino acid infusion (0.35 mmol/kg/min; 4 mg/kg/min). Day A served as a control, where no medication was given. On day B, 10 mg nifedipine, and on day C, 25 mg captopril, were administered orally before study. Without premedication (= day A, control) GFR increased from 108.0 +/- 6.9 mL/min (SEM) to 131.7 +/- 7.0 mL/min (P less than 0.05). On day B (nifedipine), GFR before stimulation by amino acids was already elevated to 121.8 +/- 4.2 mL/min (P less than 0.05 compared with day A) and increased to 132.6 +/- 6.3 mL/min with infusion of amino acids, thus to the same range as on day A without medication. On day C, after captopril, GFR did not increase with infusion of amino acids (from 112.5 +/- 7.2 to 117.3 +/- 6.3 mL/min). Our results indicate the calcium channel antagonist nifedipine and the angiotensin-converting enzyme (ACE) inhibitor captopril differ in their effect on intrarenal hemodynamic parameters. Nifedipine induces hyperfiltration at rest and allows maximal hyperfiltration to develop under amino acid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nifedipine and captopril on glomerular hyperfiltration in normotensive man. 149 65

The purpose of this study was to examine the hypothesis that the calcium channel blocker, diltiazem, modulates catecholamine-induced arrhythmias through CNS mechanisms. Rats, that had catheters previously inserted into the lateral cerebral ventricle and femoral artery, received diltiazem, 10 or 50 micrograms/kg or the diluent, into the lateral cerebral ventricle (i.c.v.). Epinephrine was infused to produce arrhythmias. The onset of ventricular arrhythmias, premature ventricular complexes, occurred at a significantly (P less than 0.05) greater dose of epinephrine, after diltiazem, compared to the control group and in a dose-dependent manner, with the mean (+/- 1 SEM) dose of epinephrine being 198 +/- 5, 175 +/- 13 and 115 +/- 15 micrograms/kg in the groups treated with 50 and 10 micrograms/kg of diltiazem and the control groups, respectively. The development of fatal arrhythmias, mainly ventricular tachyarrhythmias, occurred at significantly (P less than 0.05) greater concentrations of epinephrine with diltiazem, 50 and 10 micrograms/kg, 225 +/- 5 and 183 +/- 13 micrograms/kg, respectively, compared to controls, 131 +/- 15 micrograms/kg. Endogenous opioids of the mu-type were implicated in this action of diltiazem, because the mu opioid antagonist naloxone, 1 mg/kg (i.v.), significantly (P less than 0.05) antagonized the antiarrhythmic effects of centrally administered diltiazem and the mu opioid agonist DAGO (i.c.v.), did not further enhance the suppression of epinephrine-induced arrhythmias, produced by diltiazem, 50 micrograms/kg. Atropine sulfate, which crosses the blood-brain barrier and atropine methylnitrate, which does not enter the brain, each at 1 mg/kg (i.v.), produced an equal and significant antagonism of the effect of diltiazem, 50 micrograms/kg, that was less than that of naloxone. The combination of naloxone plus atropine sulfate completely prevented the effect of diltiazem, 50 micrograms/kg, on arrhythmias. The antiarrythmic action of diltiazem could not be explained by alteration of the blood pressure or heart rate response to epinephrine. The results suggest that: (a) calcium channels on neurons in the CNS play an important role in the modulation of epinephrine-induced cardiac arrhythmias, (b) diltiazem can suppress arrhythmias through CNS mechanisms, (c) activation of the parasympathetic nervous system mediates some of the effect of diltiazem, but (d) the mechanism of action of diltiazem is modulated through endogenous opioids.
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PMID:The calcium antagonist diltiazem has antiarrhythmic effects which are mediated in the brain through endogenous opioids. 152 99

Although sphincter of Oddi dysfunction is a recognised cause of post cholecystectomy pain, the control mechanisms involved in sphincter of Oddi function are poorly understood. Pharmacological relaxation of the sphincter of Oddi may have a beneficial effect particularly in sphincter of Oddi dysfunction where basal sphincter pressure is high. The aim of this study was to investigate the effects of calcium channel blockade (nicardipine) and synthetic cholecystokinin (ceruletide) on sphincter of Oddi pressures. Nineteen patients (median age 49 years; range 21-75) attending for routine endoscopic retrograde cholangiopancreatographic (ERCP) examination were studied. No patients with evidence of sphincter of Oddi dysfunction were included in the study. Each patient was randomly allocated to receive a three minute intravenous infusion of nicardipine 3 mg (six) ceruletide 5 ng/kg (seven) or placebo (six). Endoscopic biliary manometry was done with recording of basal sphincter of Oddi pressures, sphincter of Oddi phasic wave amplitude and frequency before and after intravenous infusions. In the nicardipine group patients showed a decrease in both basal and phasic amplitude sphincter of Oddi pressure (mm Hg) from the preinfusion values (mean (SEM)) of 24.7 (3.6) and 112.3 (13.4) to 12.9 (2.9) (p less than 0.01) and 89.9 (12.4) (p less than 0.03) after infusion respectively. Ceruletide produced a decrease in sphincter of Oddi phasic wave frequency (c/min) from 3.4 (0.3) before infusion to 2.6 (0.5) after infusion (p less than 0.05). We conclude that nicardipine effectively decreases sphincter of Oddi pressure. This drug may therefore be of value in the treatment of sphincter of Oddi dysfunction where raised sphincter pressures are thought to be the primary pathogenic feature.
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PMID:Controlled study of the effect of nicardipine and ceruletide on the sphincter of Oddi. 158 1

Left ventricular dysfunction in systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance in coronary microcirculation. We evaluated the pharmacodynamic effect of the calcium channel blocker nicardipine on left ventricular function assessed by radionuclide ventriculography in 20 patients with systemic sclerosis. Resting gated, blood-pool images were obtained at baseline and 90 min after 40 mg of oral nicardipine. The mean (+/- SEM) left ventricular ejection fraction significantly increased from 65.4 +/- 2.3% at baseline to 71.3 +/- 2.3% after nicardipine (p less than 0.005). The mean global defect score significantly decreased from 2.90 +/- 0.73 without nicardipine to 1.50 +/- 0.52 with nicardipine (p less than 0.01). The mean number of left ventricular sectors with severe hypokinesis significantly decreased from 0.80 +/- 0.24 at baseline to 0.20 +/- 0.09 after nicardipine (p less than 0.05). No significant side effects were observed with nicardipine. These results demonstrate short-term improvement in left ventricular function with nicardipine in patients with systemic sclerosis.
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PMID:Pharmacodynamic effect of nicardipine on left ventricular function in systemic sclerosis. 168 20

We screened the antiischemic, hemodynamic, and inotropic effects of different dosages of the new calcium channel blocker Ro 40-5967 in 65 patients with stable effort-induced angina pectoris. In a double-blind way, patients were randomized to recieve a single oral dose of 50, 100, or 200 mg Ro 40-5967 or placebo, given as a drinking solution. Left ventricular ejection fraction (LVEF), blood pressure (BP), and heart rate (HR) were measured at rest and during a supine bicycle exercise test on day 0 (baseline) and 2 h after drug intake on day 1. Twenty-four hours later, the bicycle exercise test was repeated. Ro 40-5967 improved exercise duration and resting LVEF. After 200 mg, exercise time increased significantly from 8.4 +/- 0.8 min (mean +/- SEM) to 9.6 +/- 0.7 min (p = 0.018), and LVEF at rest increased from 54.5 +/- 2.2 to 58.1 +/- 2.6% (p = 0.045). Time to 0.1 mV ST-segment depression increased significantly from 4.3 +/- 0.8 to 5.5 +/- 0.9 min in the 100-mg group (p = 0.013) and from 4.3 +/- 1.3 to 5.4 +/- 1.5 min in the 200-mg group (p = 0.027). Maximum ST-segment depression decreased significantly at all dose levels (p = 0.01), with the maximum decrease noted in the 200-mg group (from 0.21 +/- 0.03 to 0.15 +/- 0.02 mV, p = 0.004). BP, HR, and rate-pressure product did not change significantly at rest or at maximum exercise. A single dose of Ro 40-5967 has antiischemic properties in patients with stable angina pectoris, with maximum effects obtained after 200 mg. No signs of negative inotropy were noted, and the drug was well tolerated.
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PMID:Lack of negative inotropic effects of the new calcium antagonist Ro 40-5967 in patients with stable angina pectoris. 172 72

The understanding of the mechanisms underlying the frequency-dependent slow response excitability enhancement has been hindered by the problems inherent in multicellular preparations. These include ion accumulation/depletion in intercellular spaces and difficulties in the spatial control of transmembrane voltage. In the present communication we show that isolated ventricular cells exposed to a depolarizing (high potassium-barium containing) solution present electrophysiological properties similar to those of multicellular preparations: stable resting potential of -45.2 +/- 0.7 mV (mean +/- SEM, N = 57) in 75% of the cells and spontaneous activity in the remaining 25% (maximum diastolic potential of -41.9 +/- 1.2 mV, N = 19); high input resistance and slow response, under current clamp conditions. Under whole cell voltage clamp conditions with -45 mV holding potential, transient outward and delayed potassium currents as well as typical L type calcium channel are present. These cells also present the frequency-dependent excitability enhancement of the slow response, with the threshold stimulus at 1 Hz corresponding to about 50% of that obtained at 0.1 Hz. Thus, isolated ventricular cells constitute a suitable model for the study of frequency-dependent excitability enhancement of the slow response.
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PMID:Frequency-dependent excitability enhancement in isolated ventricular myocardial cells. 182 10

We examined the ontogeny of relaxation responses to three categories of calcium channel antagonists, represented by verapamil, diltiazem, and nifedipine, for both potential-operated (KCl-mediated) and receptor-operated channels [norepinephrine (NE)-mediated] in rat thoracic aorta. Aortic rings from 2- to 3-d, 1-wk, and 12-wk-old Sprague Dawley rats were mounted in an organ bath, bathed in Krebs' solution, and connected to a force-displacement transducer to measure isometric tension. Endothelium intact vessels at optimal passive force were exposed to a single ED50 of isotonic KCl or NE, equilibrium contraction was measured, then vessels were washed and exposed for 30 min to 1 microM verapamil, 1 microM diltiazem, or 0.1 microM nifedipine, followed by another dose of KCl or NE. Verapamil and diltiazem demonstrated significant (p less than 0.05) age-related increases in effectiveness for blocking KCl-mediated contraction [(% reduction of control contraction +/- SEM) (Verapamil: 2-3 d, 67.7 +/- 4.2; 1 wk, 72.5 +/- 1.8; 12 wk, 89.5 +/- 1.0. Diltiazem: 2-3 d, 64.6 +/- 2.9; 1 wk, 73.5 +/- 3.0; 12 wk, 83.1 +/- 1.8]. Nifedipine was equally effective at all ages: 2-3 d, 85.6 +/- 1.3; 1 wk, 90.0 +/- 1.6; and 12 wk, 91.3 +/- 1.4. Verapamil and diltiazem also showed significant age-related increases in effectiveness for blocking NE-mediated contraction (Verapamil: 2-3 d, 6.2 +/- 3.9; 1 wk, 28.0 +/- 4.8; 12 wk, 44.1 +/- 6.0. Diltiazem: 2-3 d, 8.0 +/- 3.1; 1 wk, 20.5 +/- 3.9; 12 wk, 46.5 +/- 4.8).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential ontogeny of in vitro vascular responses to three categories of calcium channel antagonists in rats. 185 81

The response properties of ampullary electroreceptors have been studied in the catfish Ictalurus nebulosus at skin temperatures between 5 and 35 degrees C. A unimodal relationship between spontaneous activity and temperature was obtained. Mean (+/- SEM) peak discharge rate was 57.3 +/- 1.8 impulses s-1 at 25 degrees C; the receptors were active at 5 degrees C (15.0 impulses s-1) and at 35 degrees C (31.5 impulses s-1). There were no dynamic responses to temperature changes in either the warming or cooling direction. The shape of the frequency characteristic depended on temperature: the peak of the gain curve shifted to low frequencies at low temperatures. There was a concomitant change of the phase characteristic: the intersection at zero degree phase angle shifted to higher frequencies with an increase of temperature, thus increasing the lead at lower frequencies and decreasing the lag at higher frequencies. Latency after combined excitatory and inhibitory impulse stimulation was temperature dependent, ranging from 16.4 ms (5 degrees C) to 5.6 ms (35 degrees C). Application of the specific calcium channel blocker menthol (0.2 mM) suppressed spontaneous activity, the effect becoming more prominent at higher temperatures. Sensitivity to sinusoidal electrical stimulation was also impaired, but to a lesser degree and mainly at lower temperatures. We conclude that the filter properties of the receptor organ can be modelled by a band-pass filter in series with a latency, both of which are temperature dependent. These filter properties might be partially based on the activation kinetics of the transduction channels.
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PMID:Ampullary electroreceptors in catfish (Teleostei): temperature dependence of stimulus transduction. 196 89


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