EFFECTS OF LOSARTAN AND ENALAPRIL ON SMALL ARTERY STRUCTURE IN HYPERTENSIVE RATS

We evaluated the effects on cardiovascular structure of the angiotensi n-converting enzyme (ACE) inhibitor enalapril and of the angiotensin I I receptor blocker losartan, administered either at hypotensive or non hypotensive dosage in spontaneously hypertensive rats (SHR). SHR were treated from ages 4 to 12 weeks with low-dose (1 mg.kg(-1).d(-1)) enal april, low-dose (0.5 mg.kg(-1).d(-1)) losartan, high-dose (25 mg.kg(-1 ).d(-1)) enalapril, or high-dose (15 mg.kg(-1).d(-1)) losartan. Untrea ted WKY and SHR were also studied. Rats were killed at 13 weeks of age , and the heart was weighed. Mesenteric small arteries were dissected and mounted on a micromyograph for determination of media thickness an d lumen diameter. In fixed arteries, cell volume, number of cells per segment length, and number of cell layers were measured using the unbi ased ''disector'' method. Systolic blood pressure was significantly re duced by the high doses of both drugs, but the hypotensive effect was greater with enalapril than with losartan (P<0.05), In the high-dose e nalapril and losartan groups, there were similar reductions in relativ e left ventricular mass, media/lumen ratio, and number of cell layers of resistance arteries; however, there were no differences in the cell volume or number of cells per segment length of resistance arteries. Low-dose enalapril did not affect systolic blood pressure or any of th e structural parameters. The results show that the hypotensive effects of both losartan and enalapril were associated with outward remodelin g of resistance arteries at the cellular level. The effect of losartan on resistance artery structure was equal to that of enalapril, despit e the smaller hypotensive effect.