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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Factors that can influence cardiovascular growth are becoming increasingly important for our understanding of such complex diseases as cardiac hypertrophy, coronary artery disease, atherosclerosis, and hypertension. Several proto-oncogenes were found to be involved in the regulation of abnormal cell growth in cardiovascular disease. It is also evident that some peptide hormones, which are well known to be involved in blood pressure control, may play a role as growth modulators. Angiotensin II is one such peptide. It elevates blood pressure through its direct vasoconstrictor, sympathomimetic, and (through release of aldosterone) sodium-retaining activity but also appears to have mitogenic actions. Interestingly, all components of the renin-angiotensin system were found locally in cardiovascular tissues. The question remains whether angiotensin can act directly as a growth factor or whether it does so indirectly by influencing or modulating cell growth factors. A better understanding of the renin-angiotensin system as a direct or indirect mediator for cardiovascular hypertrophy would offer new and interesting insights into the pathophysiology of hypertension and possibly novel options for the treatment of cardiovascular disease.
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PMID:The molecular basis of cardiovascular hypertrophy: the role of the renin-angiotensin system. 138 95

The objective of treating patients with hypertension is not simply to reduce blood pressure but rather to prevent the associated morbidity and mortality. Recent assessments of clinical trials have shown that while the risk of stroke is consistently lower with antihypertensive therapy, the same degree of success has not been demonstrated for coronary artery disease (CAD). Although there are many explanations of why we have not done as well in preventing CAD, one possibility is that the therapy used in clinical trials, primarily thiazide diuretics and beta-adrenoreceptor blockers, has increased the patient's risk of developing coronary atherosclerosis or lethal arrhythmias. Four classes of antihypertensive agents are recommended for initial therapy--thiazide diuretics, beta-adrenoreceptor blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium entry blockers. The metabolic effects of thiazide diuretics include electrolyte disturbances (hypokalemia, hypomagnesemia, and hyponatremia), dyslipidemia (increased triglycerides), abnormalities of glucose metabolism (hyperglycemia, hyperinsulinemia, and peripheral insulin resistance), and hyperuricemia. beta-Adrenoreceptor blockers have many of the same metabolic adverse reactions. beta-Adrenoreceptor blockers without intrinsic sympathomimetic activity (ISA) also cause dyslipidemias (lowered high-density lipoprotein cholesterol and increased triglycerides) and abnormalities of glucose metabolism (hyperglycemia, hyperinsulinemia, and peripheral insulin resistance). beta-Adrenoreceptor blockers with ISA and third-generation beta-blockers with selective partial agonist activity (celiprolol and dilevalol) do not cause dyslipidemia and to date do not appear to induce abnormalities in glucose metabolism. ACE inhibitors may decrease triglycerides and increase high-density lipoprotein cholesterol, and captopril may improve insulin sensitivity. Calcium entry blockers are metabolically neutral.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic considerations in the choice of therapy for the patient with hypertension. 167 Nov 90

Bopindolol is a nonselective beta blocker with mild intrinsic sympathomimetic activity. One of the drug's main benefits is its prolonged effect, lasting for 24 hours, which makes it possible to administer bopindolol in a single daily dose, a fact that may improve patient adherence to therapy. A double-blind study was performed in two centers, comparing bopindolol with metoprolol in 86 hypertensive patients. Baseline diastolic blood pressure (BP) was 100 to 120 mm Hg. The effects of bopindolol or metoprolol on BP and heart rate were similar: return to normal values was achieved in 70% of patients with either drug. A 6-month study at another center found that bopindolol did not affect the levels of total cholesterol, low-density and high-density lipoprotein cholesterol or triglycerides. Another 12-month study documented a decrease in total cholesterol, apolipoprotein (apo) A1 and apo B. The apo A/B ratio rose, thus improving the atherosclerotic index. No deterioration of glucose tolerance or immunoreactive insulin response to glucose was seen after 6 months of bopindolol administration. Bopindolol satisfactorily modifies not only resting but also exercise BP during isometric and isotonic load, thus reducing BP fluctuation during physical activities of the hypertensive patient. The drug exerts no effect on renal and liver function, electrolyte balance and hematologic parameters. Bopindolol is a very useful drug of first choice in mild and moderate hypertension. Bopindolol's main advantages include its prolonged action, good tolerance and a beneficial effect on risk factors of atherosclerosis (lipid and carbohydrate metabolism).
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PMID:Bopindolol: Czechoslovak experience with a new beta blocker in the treatment of hypertension. 167 80

It has been suggested that beta-blockers do not significantly reduce the frequency of coronary disease in hypertensives because they adversely affect the plasma lipoprotein profile. Non-selective beta-blockers cause a significant elevation of triglycerides and a reduction in the level of high-density lipoprotein. Cardioselective beta-blockers have similar, but less marked, effects. The non-selective beta-blockers with intrinsic sympathomimetic activity have little effect on the lipid profile, yet these are the least effective in reducing coronary mortality after myocardial infarction. Elevated blood flow velocity and high catecholamine levels can damage the vascular endothelium. This leads to increased permeability and the deposition of lipids. Beta-blockers reduce peak blood velocity and decrease the activity of catecholamines in plasma, which should reduce endothelial damage and the subsequent formation of plaques. Studies in animals have indeed shown that beta-blockers reduce the level of atherosclerosis, despite an elevation of serum lipids.
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PMID:Metabolic parameters: how important are pharmacologically-induced changes? 168 56

Hypertension is accompanied by 2 major types of arterial pathologic conditions: smooth muscle hypertrophy of arteriolar resistance vessels and atherosclerosis, primarily involving the larger arteries. Smooth muscle hypertrophy may develop either as a secondary defense against elevated intravascular pressure or as a primary defect responsible for the increased pressure. Insulin and a number of other trophic stimuli may play a pathogenetic role in vascular hypertrophy. Reducing blood pressure and trophic stimuli may cause hypertrophy to be reversed. Because atherosclerosis may be markedly accelerated by hypertension, especially in the presence of concomitant risk factors, such as hypercholesterolemia, cigarette smoking and diabetes mellitus, antihypertensive treatment may attenuate or even reverse the extent of atherosclerosis, but only when the causative factors are also corrected. Some commonly used antihypertensive agents, e.g., diuretics and beta blockers without intrinsic sympathomimetic activity, often aggravate hypercholesterolemia and glucose intolerance, thereby diminishing their potential protective value. Other types of drug therapy, such as alpha blockers, beta blockers with intrinsic sympathomimetic activity or other vasodilator activity, angiotensin-converting enzyme inhibitors and calcium entry blockers that may not induce biochemical changes, should provide better control of multiple risks and thereby better protection against atherosclerosis. With a better understanding of how hypertension induces arterial damage, clinicians will be able to provide more appropriate treatment and, it is hoped, alleviate such damage.
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PMID:Arterial protection: a neglected but crucial therapeutic goal. 222 Jun 48

In the submitted review the author deals with specific features of the coronary circulation, coronary reserve and importance of regulation of the tonus of the coronary arteries at their epicardiac course and the tonus at the arteriolar level. In the subsequent part the author deals systematically first with the nervous regulation incl. the basic importance of the alpha-adrenergic (vasoconstrictor) and beta-adrenergic (vaso-dilating) sympathomimetic component. He mentions also the importance of neuropeptides (neuropeptide Y and substance P). Attention is devoted to the importance of the endothelium and endothelial vasoactive substances in the control of circulation. The main representatives of substances with a vasodilatating action are the endothelial relaxation factor and prostacycline, as to vasoconstrictor substances it is endothelin, thromboxan A2 and some growth factors. The authors discuss also the mechanical component, i. e. the influence of the blood flow and viscosity on the tonus of the coronary arteries. Finally the author draws attention to the clinical importance of disorders of regulatory mechanism in atherosclerosis and some clinical entities.
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PMID:[Regulation of coronary circulation]. 225 78

The effects of 3 beta-blockers with different pharmacological properties (non-selective: propranolol; beta 1-selective: metoprolol; and with intrinsic sympathomimetic activity: pindolol) were comparatively studied on LDL and lipid metabolism in human fibroblasts. At 10(-4) M, propranolol increased low density lipoprotein binding, uptake and degradation by 1.5-, 2.2- and 1.8-fold, respectively, whereas metoprolol and pindolol had no effect. This effect of propranolol is mainly due to an increase in LDL receptor number. Propranolol also enhanced sterol, triacylglycerol, fatty acid and phospholipid synthesis by 2-3-fold from sodium acetate. Cholesterol esterification by oleic acid was significantly and specifically decreased 4-fold by propranolol. Metoprolol and pindolol affect neither sterol synthesis nor cholesterol esterification. Pretreatment of cultured fibroblasts with propranolol induced an increase in hydroxymethyl-glutaryl-coenzyme A reductase activity and a decrease in acyl-coenzyme A: cholesterol-O-acyltransferase (ACAT) activity. Propranolol inhibited the induction of ACAT activity by exogenous cholesterol. Preincubation of a cell-free extract with propranolol also induced inhibition of ACAT activity. Propranolol decreased the cholesteryl ester content of cultured cells. These effects of propranolol on LDL and cholesterol metabolism might be related to the amphiphilic properties of the drug and suggest an effect on the cholesterol intracellular traffic. The decrease in cholesterol esterification and in the cholesteryl ester cellular level induced by propranolol may be involved in its antagonizing effect on experimental atherogenesis.
Atherosclerosis 1990 Mar
PMID:The antihypertensive drug propranolol enhances LDL catabolism and alters cholesterol metabolism in human cultured fibroblasts. 232 24

The effect of pindolol (a beta-blocker with intrinsic sympathomimetic activity, ISA) on fasting plasma lipid profile in 30 hypertensive patients was compared with atenolol (without ISA) in a crossover single blind study. Both drugs lowered blood pressure. HDL-cholesterol increased significantly with pindolol (from 1.15 +/- 0.05 to 1.34 +/- 0.05 mmol/l at 12 weeks, P less than 0.001), but not with atenolol. VLDL-cholesterol increased with atenolol (from 0.57 +/- 0.09 to 0.86 +/- 0.14 mmol/l at 12 weeks, P less than 0.002), while there was no change with pindolol. These changes in lipoprotein profile suggest a more favourable effect of pindolol than of atenolol on lipid profile.
Atherosclerosis 1989 Jun
PMID:Effect of pindolol versus atenolol on lipid profile in hypertensive patients. 275 53

Plasma lipoproteins were estimated in ten hypertensive subjects (mean age 51 +/- 11.2 yr), before, 6 wk and 6 mth following treatment with Sotalol 320 mg/day. Heart rate fell sequentially throughout the study (p less than 0.01) and although there was a sequential fall in mean blood pressure this did not reach statistical significance. There was a significant increase in plasma triglyceride concentration from a basal value of 1.87 +/- 1.064 to 2.50 +/- 0.877 mmol/l (p less than 0.005) at 6 mth. No significant change was found in very low density, low density and high density lipoprotein cholesterol or apolipoprotein concentrations (Apo A-I, Apo A-II, Apo B). We conclude that Sotalol exerts a similar influence on plasma lipoproteins as other non-cardioselective beta-adrenoceptor blockers without intrinsic sympathomimetic activity and its use does not constitute an increased risk of developing atherosclerosis, when compared with other beta-blockers.
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PMID:The effect of sotalol on plasma lipoproteins and apolipoproteins. 374 22

In view of the postulated association between plasma lipids and the development of atherosclerosis, there is growing interest in the effects of beta blockers on plasma lipids. This study was undertaken to investigate whether a nonselective beta blocker, such as mepindolol, which possesses intrinsic sympathomimetic activity, causes significant changes in serum lipids, particularly in their ditribution among the different lipoproteins. Eighteen healthy subjects, twelve males and six females, were given mepindolol orally, daily doses of 0.2 mg/kg averaging 10-15 mg. Pre- and post-treatment fasting total serum cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were evaulated; the ratio LDL cholesterol/HDL cholesterol was also calculated. Total cholesterol did not change significantly after treatment with mepindolol (- 1.9 mg%), whereas a small and nonsignificant decrease was observed in LDL cholesterol (- 6 mg%); no change was found in HDL cholesterol (- 0. mg%). Serum triglycerides showed a significant increase (+ 20.9 mg%, p less than 0.01). Thus, the most prominent effect of even a short period of treatment with mepindolol is a net increase in serum triglyceride levels. It must be remembered that high triglyceride levels do not constitute a cardiovascular risk factor. On the other hand, no significant changes in total cholesterol, HDL and LDL cholesterol, and in LDL cholesterol/HDL cholesterol ratio were observed. The results of this study show that mepindolol, unlike other beta-blocking agents, does not affect cholesterol concentration and distribution among the lipoproteins. In particular it does not reduce HDL cholesterol, which is currently assumed to be inversely related to the development of atherosclerosis.
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PMID:Effect of mepindolol on serum lipids. 717 57


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