EFFECTS OF HYPERCHOLESTEROLEMIA ON THE CONTRACTIONS TO ANGIOTENSIN-IIIN THE ISOLATED AORTA AND ILIAC ARTERY OF THE RABBIT - ROLE OF ARACHIDONIC-ACID METABOLITES

The aim of this study was to investigate the effect of hypercholestero lemia on the angiotensin II-induced contractions in the isolated aorta and iliac artery of the rabbit, with respect to the role of arachidon ate metabolites, Furthermore, the effect of the angiotensin-converting enzyme inhibitor ramipril was studied On the responses to angiotensin II in the cholesterol-fed rabbit. After 12 weeks of cholesterol diet (0.3%), endothelium-dependent relaxations to acetylcholine were signif icantly fewer compared with control (30.2 +/- 5.9% vs. 73.0 +/- 1.7%) in the aorta but not in the iliac artery of the rabbit, The angiotensi n II- and methoxamine-induced contractions were also significantly low er compared with control in the aorta (101.4 +/- 6.7% vs. 60.9 +/- 4.2 % and 160.2 +/- 5.7% vs. 135.8 +/- 8.0%, respectively) but not in the iliac artery. The Lipoxygenase inhibitor nordihydroguaiaretic acid (ND GA) selectively attenuated the angiotensin II-induced contractions in rabbit aortic rings from the control group only in the presence of the endothelium, whereas it had no effect on the responses to angiotensin II in the cholesterol group (with or without endothelium). In the ili ac artery, NDGA inhibited the responses to angiotensin II in both the control and cholesterol groups. Treatment with ramipril (0.33 mg/kg/da y) significantly improved the maximal angiotensin II-induced contracti on in the aorta of rabbits fed a cholesterol diet for 16 weeks to 61.0 +/- 7.3% (vs. 32.7 +/- 9.0% in the cholesterol group). We conclude th at hypercholesterolemia leads to a reduction of angiotensin II-induced contractions in the aorta and not in the iliac artery of the rabbit. This reduction might be related to loss of endothelium-dependent lipox ygenase products and is partially reversed by ramipril.