Angiotensin converting enzyme inhibitors and expression of des-Arg9-BK (kinin B1) receptors in vivo.
The effect of the selective kinin B1 receptor agonist des-Arg9-BK was studied on blood pressure and on the in vitro aorta of rabbits pretreated 18 h earlier with lipopolysaccharide from E. coli, an infusion of bradykinin or with one of three angiotensin converting enzyme inhibitors captopril, enalapril or teprotide. The hypotensive response in vivo and contractile response seen on the in vitro aorta was selectively increased to des-Arg9-BK in all pretreated groups compared to controls, effects which were blocked by the selective competitive kinin B1 receptor antagonist des-Arg9-[Leu8]BK. Dexamethasone given to lipopolysaccharide pretreated rabbits had no effect on the increased hypotensive response seen with des-Arg9-BK. The skin vascular permeability response to des-Arg9-BK, bradykinin and histamine remained unchanged in the groups pretreated with lipopolysaccharide or captopril compared to controls. The possible mechanism(s) whereby angiotensin converting enzyme inhibitors produce this effect and the possible relevance to the inflammatory side-effects seen with this group of drugs is discussed.
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Department of Physiological Sciences, Medical School, University of Manchester, U.K.
Whalley
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D000109:Acetylcholine / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007705:Kinins / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D003907:Dexamethasone; D000803:Angiotensin I; D000109:Acetylcholine; D009638:Norepinephrine