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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormalities in sodium homeostasis and in atrial natriuretic peptide (ANP) behavior could play a role in determining and accelerating the development of glomerular hypertension, hypertension, and microalbuminuria in insulin-dependent diabetes. The aim of the present study was to investigate in 32 hypertensive insulin-dependent diabetic patients (HD) with an altered albumin excretion rate the natriuretic response and ANP release to saline load (2 mmol/kg 90 min, and the effects angiotensin converting enzyme inhibitor therapy 2.5 to 5.0 mg cilazapril, once daily), and calcium antagonists (sustained release verapamil: 120 to 240 mg Isoptin Press, once daily, and long acting nifedipine: 20 to 40 mg Adalat AR, twice daily) on sodium homeostasis and albumin excretion rate. Eight normal subjects matched for sex, age, and weight served as controls. The 32 HD patients showed a blunted response in ANP release and sodium excretion during saline infusion in comparison with controls. The cilazapril and verapamil treatments were tested in 16 of the 32 HD patients and were both effective in ameliorating natriuretic and ANP response to saline load and in decreasing albumin excretion rate. The combined cilazapril and verapamil treatment further improved both these parameters in these patients, although blood pressure levels were comparable. The other 16 HD patients underwent sequential verapamil and nifedipine treatment. Verapamil was more effective than nifedipine in improving natriuresis and ANP release to saline load and in lowering the albumin excretion rate. The results of the present study demonstrate that sodium homeostasis and ANP release are altered in hypertensive nephropathic patients, and both cilazapril and verapamil are more effective than nifedipine in ameliorating natriuresis, ANP release, and albumin excretion rate.
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PMID:Effects of angiotensin converting enzyme inhibitors and calcium antagonists on atrial natriuretic peptide release and action and on albumin excretion rate in hypertensive insulin-dependent diabetic patients. 145 87

Verapamil, the first calcium-channel blocker to be introduced for clinical use, is a major drug used for the treatment of systemic hypertension. During the past 10 years, the use of verapamil for hypertension has produced a considerable clinical database to support the efficacy and safety of the agent in many patients. Because of its short half-life, verapamil was originally administered 3 to 4 times daily. During the past decade, a sustained-release formulation of verapamil has been marketed in the US. This product allows for once-daily dosing up to 240 mg/d; however, when higher doses are needed, this sustained-release formulation should be administered twice daily. In addition, the medicine should be taken with food to avoid the high peak blood levels of verapamil, which appears to be related to the delivery system. A new pellet-filled capsule formulation of verapamil (Verelan, Lederle, Wayne, NJ and Wyeth-Ayerst, Philadelphia, PA) is available and provides controlled absorption, 24-hour blood pressure control, improved peak-to-trough plasma levels, and once-daily dosing regardless of dosage size. Prolonged-release verapamil can be taken without food.
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PMID:Sustained-release verapamil formulations for treating hypertension. 158 64

The relatively short half life of verapamil necessitates divided daily dosing in the treatment of angina, hypertension and arrhythmia. To reduce dosing frequency and increase patient compliance and therapeutic efficacy, a controlled-release once-daily verapamil formulation (Verelan) has been developed in three dosage strengths, 120 mg, 240 mg and 360 mg. In order to investigate the dose linearity of this formulation in the 120 mg and 360 mg dose range, un unblinded, crossover, comparative evaluation of the three dosage strengths was performed in a population of 27 male volunteers. Each treatment period lasted nine days with a minimum of 7 days between periods. On Days 1 and 2 of each treatment period, the single dose phase was evaluated following administration of medication on Day 1 only with regular blood sampling over the 48 hour period. On Days 3 and 7 inclusive, the five-day steady phase was evaluated. Mean plasma profiles following administration of each dose demonstrated extended verapamil absorption up to 24 hours after dosing. In both the single dose and steady state phases a linear relationship was observed between increasing dose and pharmacokinetic response over the dose range of 120 mg and 360 mg. This linearity in response with increasing dose is in contrast to the non-linearity of verapamil's pharmacokinetics with conventional verapamil formulations previously described by an number of workers and may be due to a saturation of verapamil's hepatic first pass metabolic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dose proportionality of pharmacokinetics with a cr-verapamil formulation. 182 Aug 98

Studies were carried out to examine the relationship between blood pressure lowering using the Ca2+ channel blocker verapamil, and regression of ventricular hypertrophy, in the spontaneously hypertensive rat (SHR). Untreated male SHR showed rapidly developing hypertension (systolic pressure 194 +/- 2 mm Hg, 109 days of age) and moderate ventricular hypertrophy. Verapamil (Calan-SR, G.D. Searle Co.) treatment for 30 days at maximum doses of 18.7 and 49.9 mg/kg per day supplied in the food, lowered blood pressure maximally 37 mm Hg. The drug had no effect on heart rate. Decrease in the mass of the left ventricle plus interventricular septum was positively correlated with the verapamil-induced decrease in blood pressure (r = 0.69, P less than 0.001). SHR exposed continuously to 500 ppm carbon monoxide (CO) for 30 days showed a similar decrease in blood pressure (33.0 mm Hg). Such SHR, however, displayed increases in mass of the left ventricle plus septum and right ventricle, and of hematocrit, nearly identical to same age Sprague-Dawley rats similarly exposed to CO. Neither verapamil nor CO treatment altered myocardial water content. The results suggest that a modest lowering of blood pressure with verapamil in the SHR produces a relatively rapid decrease in left ventricular mass. It also shows that even when afterload is reduced in the SHR, as with CO, substantial ventricular hypertrophy develops, probably because of augmented preload, and that it is comparable to that produced in non-hypertensive rats.
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PMID:Effects of verapamil and carbon monoxide on blood pressure and heart mass in the spontaneously hypertensive rat. 214 23

Treatment of hypertension may prevent many of the complications attributable to blood pressure elevation, particularly those that are "pressure-related," such as stroke. However, the atherosclerotic complications of hypertension, e.g., coronary artery disease manifested as coronary morbidity and mortality, have not been reduced significantly with antihypertensive therapy. This disappointing outcome may reflect the adverse metabolic effects of the traditional therapies, diuretics and beta blockers, and their lack of specific vasoprotective properties. Increasing attention is thus being paid to the newer antihypertensive agents, which typically have fewer adverse effects and perhaps more physiologic mechanisms of antihypertensive action. Since calcium plays a key role in the genesis of atherosclerosis, calcium antagonists may positively affect the course of vascular disease. Investigators have observed that calcium antagonists display clear antiatherosclerotic properties in experimental as well as clinical studies. In one recently published clinical study, coronary artery disease was shown to develop more slowly, with a slower progression of individual stenoses, higher regression rate and less frequent occurrence of new lesions in patients treated chronically with verapamil compared to those receiving conventional therapies. Other similar investigations are currently under way to evaluate the antiatherogenic properties of calcium antagonists, including the Frankfurt Isoptin Progression Study (FIPS), the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS), the International Nifedipine Trial on Atherosclerosis Coronary Therapy (INTACT), and the large-scale Montreal Heart Institute Study. Results of these studies, which use precise end points such as myocardial infarction, cerebral infarction and peripheral vascular disease, may revolutionize the treatment of hypertension by identifying therapeutic approaches that control both the pressure-related and atherosclerotic complications of the disease.
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PMID:Anti-atherosclerotic and vasculoprotective actions of calcium antagonists. 225 66

Verapamil HCl was chronically administered to inbred Dahl S/JR and R/JR rats maintained on a diet containing 8.0% NaCl (w/w) and the effects on blood pressure (BP) and heart rate (HR) were investigated. Treatment over a 4-week period via implanted miniosmotic pumps attenuated but did not prevent the development of salt-induced hypertension (HT) in the S/JR rat. Elevated HR, possibly reflexive in origin, was observed in S/JR rats that received verapamil but not in similarly treated R/JR rats. Although verapamil retarded the development of HT in S/JR rats, BP rose to moderately hypertensive levels, and the ventricle/body weight ratio was elevated by the termination of the study. The effect of verapamil on the density and affinity of alpha 1-, alpha 2-, and beta-adrenergic, muscarinic cholinergic, and calcium channel receptors in renal and ventricular membranes was also assessed. The density of renal and ventricular alpha 1- and beta-adrenoceptors was not affected by chronic drug treatment. The density of renal alpha 2- and beta-adrenoceptors was greater in the S/JR strain than in the R/JR strain, regardless of the treatment. The density of muscarinic cholinergic and calcium channel receptors in the ventricle was not affected by the treatment. The results of this study suggest that the long-term antihypertensive effects of verapamil in the S/JR rat do not involve an alteration in the binding characteristics of adrenergic, cholinergic, or calcium channel receptor sites in ventricular and renal membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium channel blockade with verapamil. Effects on blood pressure, renal, and myocardial adrenergic, cholinergic, and calcium channel receptors in inbred Dahl hypertension-sensitive (S/JR) and hypertension-resistant (R/JR) rats. 245 14

In an open multicenter trial (uncontrolled study) in 4,247 patients (49.1% male, 50.9% female; aged 17-89 years) with mild, moderate, or severe hypertension, the antihypertensive efficacy and in particular the tolerability of verapamil slow-release (SR) 240 mg (Isoptin RR) were studied. The dosage of the drug was adjusted to the therapeutic response; in 88.7% of the patients it was titrated according to the study protocol: 63.2% received constantly one SR tablet throughout the 6-week treatment period; in 15.6% the dosage was increased to one and a half tablet after 2 weeks, and in 9.9% to one tablet b.i.d. after a further 2 weeks. Monotherapy with verapamil SR 240 mg normalized diastolic blood pressure (less than or equal to 90 mm Hg) in 90% of the patients with mild hypertension, 77% of those with moderate, and 61% of those with severe hypertension. It was evident that blood pressure reduction was more pronounced the higher the baseline value. Cardiac and extracardiac tolerability of verapamil SR 240 mg was good. Mean heart rate was slightly reduced, none of the patients developed a second- or third-degree atrioventricular block. Side effects were reported by 480 of the 4,247 patients (11.3%). As expected, constipation (4.03%) was the predominant adverse reaction, followed by dizziness (3.65%), headache (1.54%), and other (less than 1%). In 217 patients (5.1%) therapy was discontinued prematurely, in 139 (3.27%) because of side effects.
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PMID:Efficacy and safety of verapamil SR 240 mg in essential hypertension: results of a multicentric phase IV study. 247 86

The efficacy, safety and toleration of sustained release verapamil (Securon SR, Knoll) and long acting propranolol (Inderal LA, ICI) in the treatment of mild to moderate hypertension were compared in a randomized, double-blind, parallel group study. Both drugs were of similar efficacy and were well tolerated in the majority of patients. However, in the verapamil SR treated group side-effects resulted in significantly fewer drug-related withdrawals.
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PMID:Verapamil SR and propranolol LA: a comparison of efficacy and side effects in the treatment of mild to moderate hypertension. 306 7

The effectiveness of hypotensive action and tolerance of Isoptin SR-240 were studied in 20 patients with primary arterial hypertension. The drug was used in doses 240-360 mg daily (mean dose 324 mg daily). Blood pressure returned to normal values in 12 (60%) out of 20 patients. In the remaining eight cases no blood pressure normalization was achieved. Side effects occurred in five patients. General worsening of wellbeing and easy tiring were most frequently observed. The results of the present work indicate that Isoptin SR-240 is an effective hypotensive drug, useful in the treatment of mild and moderate arterial hypertension.
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PMID:[Use of isoptin SR-240 in treatment of hypertension]. 790 Mar 85

Stress-induced hemodynamic and hemostatic responses may acutely trigger atherosclerotic plaque disruption and thrombosis leading to myocardial infarction. This study was designed to evaluate the responses to three stressors and to determine if once-daily sustained release verapamil (Verelan) modified these responses. We studied 13 patients with mild to moderate hypertension in a randomized, double-blind, placebo-controlled crossover trial. After 4 weeks of therapy, patients were evaluated following assumption of the upright posture, mental stress, and cold pressor test. During placebo, the stressors produced an increase in systolic pressure (144 +/- 2 to 167 +/- 3 mmHg, p < 0.001), heart rate (70 +/- 2 to 77 +/- 2 beats/ min, p < 0.001), and platelet aggregability to adenosine diphosphate (threshold concentration fell from 2.8 +/- 0.4 to 1.9 +/- 0.1 microM, p = 0.05) and epinephrine (3.4 +/- 0.9 to 1.6 +/- 0.6 microM, p < 0.001). Verapamil lowered systolic pressure at baseline (144 +/- 2 to 134 +/- 2 mmHg, p < 0.001), and after stress (167 +/- 3 to 154 +/- 3 mmHg, p < 0.001), but did not alter the absolute increase with stress. During verapamil, platelet reactivity did not increase with stress, and the post-stress response to epinephrine was reduced (higher threshold concentration) compared with placebo (3.9 +/- 1.3 vs. 1.5 +/- 0.3 microM, p = 0.05). Verapamil also reduced the response to collagen (increased lag time) at baseline and after stress (111 +/- 9 vs. 91 +/- 3 s, p < 0.01). We conclude that verapamil blunted potentially harmful stress-induced hemodynamic and hemostatic changes. Further studies are required to determine whether these effects translate into a lower incidence of acute cardiovascular events.
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PMID:Stress-induced hemodynamic and hemostatic changes in patients with systemic hypertension: effect of verapamil. 867 57


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