Anti-inflammatory agents in experimental atherosclerosis. Part 2. Failure of antihypertensive drugs to exacerbate atherosclerotic plaque formation.
Hypertension is associated with an increased incidence of generalized vascular disease. Antihypertensive drug therapy, while decreasing overall mortality due to cerebral hemorrhage, myocardial hypertrophy or renal failure, paradoxically does not appear to reduce the incidence of coronary atherosclerosis. This study investigates whether the drugs, as a possible side effect, may have an adverse influence on the development of atherosclerotic plaques. Groups of rabbits were fed an atherogenic diet containing 1% cholesterol for 12 weeks. Two commonly used antihypertensive agents (methyldopa and chlorthalidone) were added to the diet of some groups at levels of 100 mg and 10 mg per day respectively. No significant increase in total atherosclerotic plaque area was produced by either of the drugs tested singly or in combination. Plasma renin levels were only mildly elevated and in this experimental system there was no correlation between renin activity and atherosclerotic plaque intensity. There is thus no evidence from this study that antihypertensive drugs have any adverse effects on atherosclerotic plaque formation. While the ineffectiveness of these drugs against coronary atherosclerosis may indicate that normalization of pressure cannot arrest changes already initiated, it also supports the possibility that association of atherosclerosis with hypertension may be symptomatic of a common underlying defect not correlated by normalizing blood pressure.
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced* / Q000473:pathology; D002752:Chlorthalidone / Q000008:administration & dosage / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008750:Methyldopa / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D012083:Renin / Q000097:blood
D002791:Cholesterol, Dietary; D008750:Methyldopa; D002784:Cholesterol; D012083:Renin; D002752:Chlorthalidone