title: Effects of hypercholesterolemia on the contractions to angiotensin II in the isolated aorta and iliac artery of the rabbit: role of arachidonic acid metabolites.
abstract: The aim of this study was to investigate the effect of hypercholesterolemia on the angiotensin II-induced contractions in the isolated aorta and iliac artery of the rabbit, with respect to the role of arachidonate 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 significantly 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 angiotensin II- and methoxamine-induced contractions were also significantly lower 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 (NDGA) 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 iliac artery, NDGA inhibited the responses to angiotensin II in both the control and cholesterol groups. Treatment with ramipril (0.33 mg/kg/day) significantly improved the maximal angiotensin II-induced contraction 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 that 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 lipoxygenase products and is partially reversed by ramipril.
authors.affiliation: Utrecht University, Faculty of Pharmacy, Department of Pharmacoepidemiology & Pharmacotherapy, The Netherlands.
authors.forename: J P
authors.initials: JP
authors.lastname: Dam
authors.forename: W
authors.initials: W
authors.lastname: Vleeming
authors.forename: J
authors.initials: J
authors.lastname: Riezebos
authors.forename: M J
authors.initials: MJ
authors.lastname: Post
authors.forename: A J
authors.initials: AJ
authors.lastname: Porsius
authors.forename: J
authors.initials: J
authors.lastname: Wemer
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D016718:Arachidonic Acid / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006937:Hypercholesterolemia / Q000378:metabolism / Q000503:physiopathology*; D007083:Iliac Artery / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D011817:Rabbits; D017257:Ramipril / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002791:Cholesterol, Dietary; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D016718:Arachidonic Acid; D009637:Masoprocol; D017257:Ramipril; D007213:Indomethacin