title: Vasomotor responses in cyclosporin A-treated rats after chronic angiotensin blockade.
abstract: Chronic angiotensin-converting enzyme (ACE) inhibition prevents endothelial dysfunction in hypertension and hypercholesterolemia. Long-term treatment with cyclosporin A impairs endothelium-dependent relaxations and augments contractions to angiotensin II in the rat aorta. The present study compares vasomotor responses to several vasoconstrictor and dilator stimuli after 6 weeks of oral treatment with either the angiotensin-converting enzyme inhibitor lisinopril (10 mg/kg per day), the angiotensin subtype 1 receptor antagonist D 8731 (10 mg/kg per day), cyclosporin A (15 mg/kg per day), or a combination of cyclosporin A with lisinopril or D 8731 (n = 15 rats per group). Twenty-four hours after the last treatment, aortic rings were mounted in organ chambers for measurement of isometric force. Endothelium-dependent relaxations to acetylcholine and calcium ionophore were impaired by cyclosporin A but not affected by the vasodilators. Cyclosporin A-induced endothelial dysfunction was prevented by cotreatment with lisinopril or D 8731. Relaxations to nitroglycerin, SIN-1, and forskolin were not affected by any treatment. Contractions to phenylephrine and serotonin were reduced by lisinopril but not by D 8731. In contrast, contractions to angiotensin II were augmented by cyclosporin A, lisinopril, and the combination of both but not by D 8731 or D 8731 plus cyclosporin A. The data suggest a role for angiotensin II in cyclosporin A-induced endothelial dysfunction. Chronic ACE inhibition reduces overall smooth muscle contractility. The selective augmentation of angiotensin II effects by ACE inhibition and cyclosporin A suggests upregulation of angiotensin receptors in the aortic smooth muscle by these treatments. Chronic angiotensin subtype 1 receptor blockade does not appear to affect angiotensin receptor function.
authors.affiliation: Department of Cardiology, German Heart Institute Berlin.
authors.forename: W
authors.initials: W
authors.lastname: Auch-Schwelk
authors.forename: E
authors.initials: E
authors.lastname: Duske
authors.forename: U
authors.initials: U
authors.lastname: Hink
authors.forename: M
authors.initials: M
authors.lastname: Betz
authors.forename: M
authors.initials: M
authors.lastname: Unkelbach
authors.forename: E
authors.initials: E
authors.lastname: Fleck
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology* / Q000633:toxicity; D006321:Heart / Q000033:anatomy & histology; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D017706:Lisinopril / Q000494:pharmacology; D008099:Liver / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001713:Biphenyl Compounds; D011804:Quinolines; D000804:Angiotensin II; C081112:ICI D8731; D016572:Cyclosporine; D017706:Lisinopril