Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently it has been recognized that coronary vasospasm plays a significant role in precipitating myocardial ischemic pain in a significant minority of individuals with coronary atherosclerosis (approximately 27-35% of patients with angina pectoris at rest). In these individuals normal physiological vasoconstrictor stimuli appear to trigger a spasm of the large epicardial coronary vessels; evidence suggests that it may be caused by the release of increased amounts of calcium from augmented sarcolemmal storage sites. The calcium entry blockers are remarkably effective in preventing coronary spasm by reducing intracellular calcium, but by different mechanisms. Verapamil appears to reduce intracellular and, more specifically, sarcolemmal calcium stores directly. Diltiazem appears to reduce intracellular calcium by stimulating the sarcolemmal sodium-potassium pump and reducing intracellular sodium, and by this mechanism. potentiating passive sodium-calcium exchange. The effects of the calcium entry blockers on myocardial contractility, cardiac pacemaker and conduction tissue, and regional vascular smooth muscle are also different. This makes some of these agents more suitable than others for therapy of other clinical problems such as chronic stable angina pectoris, supraventricular tachycardia, hypertension, hypertropic cardiomyopathy, and protection of the ischemic myocardium during cardiac surgery.
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PMID:Clinical use of calcium entry blockers. 730 98

The Joint National Committee Reports IV (1988) and V (1992) have emphasized individualization of drug therapy for patients with hypertension-a departure from the "stepped" care approach of initiating therapy with diuretics as advocated by the JNC I-III in the 1970's and 1980's. This review highlights individualization or "patient profiling" using calcium channel blockers as first-line treatment strategy for patients with primary hypertension--especially in the patient who has attendant risk factors and sequelae. The calcium channel antagonists, especially effective in elderly and Black patients, have proven efficacy in reducing left ventricular hypertrophy and improving diastolic function in patients with hypertensive heart disease. The heart rate limiting calcium antagonist, verapamil, has been found effective in outcome trials of reducing death and reinfarction rates post myocardial infarction and is an alternative therapy for the beta blocker intolerant hypertensive post myocardial infarction. More vascular specific dihydropyridines (felodipine, isradipine, and amlodipine) may be preferable to rate limiting agents in hypertensives with sinus node or AV conduction disorders and in those with impaired left ventricular systolic function. Verapamil and diltiazem have been effective in preliminary trials in reducing proteinuria and preserving renal function in both diabetic and non diabetic hypertensives. Calcium channel antagonists appear to prevent the progress of atherosclerosis independent of their antihypertensive properties. Further, they have theoretic value in improving endothelial mediated vasodilation.
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PMID:Individualization of therapy for hypertension in the 1990's: the role of calcium antagonists. 785 64

Microvascular and macrovascular complications are a major cause of increased morbidity and mortality in patients with diabetes mellitus and hypertension. Atherosclerosis is the major cause of these complications. Recently, Hebden and colleagues demonstrated endothelial injury in a rat model with streptozotocin-induced diabetes mellitus and deoxycorticosterone acetate-induced hypertension. To determine if captopril and verapamil reduce endothelial injury in this model of diabetic hypertensive (DH) rats, we evaluated mean medial thickness and intimal cell changes in four groups of rats: control, untreated DH rats, captopril-treated DH rats, and verapamil-treated DH rats. Mean medial thickness increased from 63.5 +/- 4.8 microns in control rats (n = 7) to 107.2 +/- 7.5 microns in untreated DH rats (n = 8), (P < .05). Verapamil and captopril blunted DH-induced medial thickening to 90.1 +/- 4.9 and 93.7 +/- 8.3 microns, respectively (P < .05 compared with control and untreated rats). An endothelial injury index (EI), consisting of white blood cells adhered to the intimal surface and rounded endothelial cells per 25-microns arc in aortic vessels, was determined for each group. The EI increased from 0.2 +/- 0.1 cells/25-microns arc in control rats to 6.3 +/- 4.0 cells/25-microns arc in untreated DH rats. Both verapamil and captopril diminished the EI in DH rats to 0.8 +/- 0.2 and 2.7 +/- 0.3 cells/25-microns arc, respectively (P < .05 compared with untreated DH rats). In addition, verapamil decreased the EI in DH rats to a greater degree than captopril (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of verapamil and captopril on endothelial injury in the diabetic hypertensive rat. 794 65

The VHAS (Verapamil-Hypertension Atherosclerosis Study) Investigators entered 1464 patients with essential hypertension and blood pressure (BP) values > or = 160 mmHg systolic and 95 mmHg diastolic (DBP) but excluded those with a DBP > or = 115 mmHg, and those with diabetes mellitus or previous myocardial infarction or cerebrovascular episodes. Patients were randomly allocated to drug therapy for 2 years with either slow-release verapamil 240 mg once daily or chlorthalidone 25 mg once daily, with nonresponders receiving additional captopril 25 mg daily. A random group of eligible patients (n = 494) was followed for a more extended period (4 years) using beta-mode ultrasound. The end point is the development of atherosclerosis detected by ultrasound imaging. The most interesting observation thus far is that in this population of middle-aged hypertensives without a history of previous cardiovascular events, about two thirds had asymptomatic carotid alterations. The study is ongoing.
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PMID:Vascular complications in hypertension: the VHAS study. Verapamil-Hypertension Atherosclerosis Study. 856 70

1. Intimal thickening is a common site for atherosclerosis. Therefore, we investigated whether the calcium entry blocker verapamil (10 mg kg-1 body weight day-1, s.c.) can retard intimal thickening and changes in vascular reactivity induced by a non-occlusive, silicone collar positioned around the left carotid artery of rabbits. The contralateral carotid artery was sham-operated and served as a control. 2. Verapamil and placebo (saline 0.1 ml kg-1, day-1, s.c.) treatments were initiated 7 days before placing the collar and lasted 3 weeks. Thereafter, segments were cut from collared and sham-treated arteries for histology and isometric tension recording. 3. The intima/media (I/M ratio increased after 14 days of collar treatment, but intimal thickening was not inhibited by verapamil (I/M ratio placebo 0.31 +/- 0.07, verapamil 0.32 +/- 0.09). 4. The collar decreased the capacity to develop force, as indicated by the response to a supramaximal concentration of KCl, decreased the sensitivity (pD2) to acetylcholine (ACh) and phenylephrine (Phe), but increased the sensitivity to 5-hydroxytryamine (5-HT). 5. Although verapamil did not affect intimal thickening, it normalized the hypersensitivity to 5-HT in collared arteries. 6. The contraction to the supramaximal concentration of KCl was not affected by verapamil. Verapamil decreased the Emax of ACh, but this was only seen in collar-treated arteries. Verapamil also decreased the sensitivity to ACh and Phe, in both sham- and collar-treated arteries. 7. We conclude that verapamil, without preventing thickening of the intima, can modify collar-induced changes in vascular reactivity.
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PMID:Effect of verapamil on intimal thickening and vascular reactivity in the collared carotid artery of the rabbit. 884 32

The involvement of inflammatory mechanisms in the progression of atherosclerosis has recently been suggested. Monocyte chemotactic protein 1 (MCP-1) is a soluble protein which is implicated in acute and chronic inflammatory processes, including atherosclerosis. We evaluated the effect of human recombinant MCP-1 on the in vitro proliferation of rat vascular smooth muscle cells (VSMCs). Incubation of VSMCs with MCP-1 (50-200 ng/ml) in the presence of 0.5% FCS significantly increased cell proliferation, [3H]-thymidine incorporation and the proliferative S fraction, measured by flow cytometry, compared to control cells. The proliferative effect of MCP-1 was specific, as shown by inhibition with a rabbit polyclonal serum to MCP-1. Moreover, the mitogenic effect of MCP-1 was significantly inhibited by downregulation of protein kinase C (PKC) activity and by incubation with H-7, a protein kinase inhibitor, suggesting the involvement of the PKC system. Verapamil, a Ca2+ channel blocker, also reduced the stimulatory effect of MCP-1 on cell proliferation. This study demonstrates that MCP-1 does not merely have a chemotactic activity, but also a mitogenic effect on cultured rat VSMCs.
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PMID:Monocyte chemotactic protein 1 (MCP-1) is a mitogen for cultured rat vascular smooth muscle cells. 907 26

Relationships between apolipoproteins and other lipid parameters and cardiovascular (CV) prognosis were evaluated in the Angina Prognosis Study In Stockholm (APSIS). Out of 809 patients with stable angina pectoris, lipid variables were obtained in 786 patients at baseline, and after one month's double-blind treatment with metoprolol or verapamil, to evaluate treatment effects on these lipid variables. During a median follow-up time of 3.3 years (2663 patient years), 37 patients suffered a CV death, 30 suffered a non-fatal myocardial infarction (MI) and 100 underwent a revascularization. Apolipoprotein (apo) A-I, high-density lipoprotein cholesterol and triglycerides were predictors of CV death or non-fatal MI in univariate analyses, but only apo A-I remained as an independent predictor in multivariate analyses. All lipid variables except low density lipoprotein cholesterol were related to the risk of revascularization in univariate analyses, but only apo A-I and apo B were independent predictors of such events. Triglycerides were weakly, but not independently, associated with prognosis. Verapamil and metoprolol had differential short-term effects on lipids, with a shift towards a more atherogenic profile in metoprolol treated patients. However, there was no significant impact of the treatment given, or of these treatment effects on the risk of CV events. Results of the present study suggest that apolipoprotein levels were better predictors of CV events than other lipid parameters in patients with stable angina pectoris.
Atherosclerosis 1997 Nov
PMID:Cardiovascular prognosis in relation to apolipoproteins and other lipid parameters in patients with stable angina pectoris treated with verapamil or metoprolol: results from the Angina Prognosis Study in Stockholm (APSIS). 939 79

In response to activation of phagocytic cells and during inflammatory disorders, some proteases and very reactive oxygen species are produced. These proteases and oxidants are involved in many diseases like tissue injury or atherosclerosis. We have shown in vitro that verapamil, a calcium channel blocker, had antielastase and antioxidant properties. This drug inhibited the release of elastase by neutrophils in a dose-dependent manner when these cells were stimulated by phorbol-myristate-acetate (PMA), by N-formyl-methionyl-leucylphenylalanine (fMLP) and by the calcium ionophore A23187 (Ca.I). In addition, verapamil inhibited superoxide anion when human neutrophils were stimulated by PMA, fMLP, dioctanoylglycerol (DiC8), Ca.I or by opsonised zymosan (OZ). Verapamil did not act by scavenging elastase or oxidants as demonstrated in cell-free models which showed no direct antielastase or antioxidant effect involved by verapamil. Superoxide anion and elastase inhibition by verapamil has been considered to the mobilization of cytosolic calcium and inhibition of protein kinase C. The results suggest that verapamil might contribute help the development and progression of atheroma where oxidants and elastase are involved.
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PMID:Verapamil inhibits elastase release and superoxide anion production in human neutrophils. 951 2

Increased inflammatory activity and platelet activation have been associated with an increased risk of cardiovascular (CV) events in epidemiological studies, but their prognostic importance in patients with stable angina pectoris is less well established. The Angina Prognosis Study in Stockholm (APSIS), comprised 809 patients (2766 patient years) with stable angina pectoris on double-blind treatment with verapamil or metoprolol. Plasma levels of fibrinogen and orosomucoid (an acute phase reactant), white blood cell counts (WBC), platelet counts and the urinary excretion of beta-thromboglobulin (reflecting platelet secretion), were related to the risk of CV death (n=36), non-fatal myocardial infarction (MI) (n=30) or revascularization (n=99) in a subgroup of 782 patients. Verapamil and metoprolol had only minor effects on the inflammatory variables. In multivariate Cox regression analyses (adjusted for previous MI, hypertension, diabetes mellitus and smoking), fibrinogen and WBC were independent predictors of CV death or non-fatal MI, as well as the risk of revascularization. Orosomucoid did not carry any independent information. Platelet counts and urinary beta-thromboglobulin were not significantly related to CV prognosis. The treatment given did not significantly influence the prognostic impact of either fibrinogen or WBC. Fibrinogen and WBC were independent predictors of CV death or non-fatal MI as well as disease progression leading to revascularization in patients with stable angina pectoris. As fibrinogen is also an acute-phase reactant, the present findings indicate that inflammatory activity is involved in disease progression in stable angina pectoris.
Atherosclerosis 2000 Jan
PMID:Inflammatory and hemostatic markers in relation to cardiovascular prognosis in patients with stable angina pectoris. Results from the APSIS study. The Angina Prognosis Study in Stockholm. 1058 Jan 84

Verapamil, the oldest calcium-channel blocker, is now being rediscovered and reevaluated in the light of new novel drug delivery systems and new evidence-based trials. Verapamil, a phenylalkylamine, is useful in the treatment of hypertension, stable angina, and narrow QRS supraventricular arrhythmias. This calcium antagonist is effective in both young and old, and both black and white hypertensive patients, and is free of metabolic side effects. Verapamil has a well-documented history as an effective antianginal agent when directly compared with a beta-blocker, and is more effective in reducing myocardial ischemia compared with amlodipine monotherapy. Because of the short half-life of verapamil, drug delivery systems are used to prolong the duration of action. Novel drug delivery systems using encapsulated beads or a modified osmotic pump have been designed to be taken at nighttime to provide maximal blood pressure reduction in the early morning hours and effective 24-hour blood pressure control, and to avoid excessive blood pressure reduction during sleep. The Verapamil in Hypertension and Atherosclerosis Study has documented equivalent effectiveness of verapamil compared with chlorthalidone, but showed superior plaque regression and reduced events in subjects with the greatest plaques with verapamil treatment. The Angina Prognosis Study in Stockholm, comparing verapamil and metoprolol for stable angina, found no difference in total cardiovascular mortality or combined cardiovascular events. Other large ongoing randomized, multicenter trials, including Controlled-Onset Verapamil Investigation of Cardiovascular Endpoints and the International Verapamil-Trandolapril Study, will expand our knowledge of the role of verapamil in the treatment of hypertension.
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PMID:Verapamil revisited: a transition in novel drug delivery systems and outcomes. 1197 70


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