Enhanced reactivity to bradykinin, angiotensin I and the effect of captopril in the pulmonary vasculature of chronically hypoxic rats.
We compared the reactivity of pulmonary vessels to bradykinin (BK) and angiotensin I (AI) in normal and chronically hypoxic rats; the latter have pulmonary hypertension and muscularized pulmonary arterioles. These peptides are respectively inactivated and activated by the angiotensin converting-enzyme (ACE) on pulmonary endothelium. Isolated lungs were perfused at a constant flow rate when changes in pulmonary artery pressure (Ppa) reflect changes in vascular resistance. Dose-response curves to BK (1 ng-10 micrograms) were derived during normoxia and pre-constriction by hypoxia; BK both decreased and increased vascular resistance, i.e. vasodilation and vasoconstriction. In normal rats only constriction was seen in normoxia, which reflected low basal vascular tone, whereas in chronically hypoxic rats there was only dilatation which reflected high basal vascular tone. In hypoxia in normal rats, low doses caused dilatation, high doses constriction; in chronically hypoxic rats there was again only dilatation which was larger than in controls. After the ACE-inhibitor captopril, constriction was exaggerated in control rats in both normoxia and hypoxia and took place in chronically hypoxic rats after high doses in both normoxia and hypoxia; oedema often followed. Dose-response curves to AI (1 ng-micrograms) in normoxia showed greatly enhanced pressor responses in chronically hypoxic compared with normal rats, probably attributable to increased sensitivity to angiotensin II (AII) rather than enhanced conversion of AI to AII. Captopril caused a proportionate reduction in responses in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Russell
P C
PC
University Dept of Medicine, Royal Hallamshire Hospital, Sheffield, UK.
Emery
C J
CJ
Cai
Y N
YN
Barer
G R
GR
Howard
P
P
D000803:Angiotensin I / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology* / Q000627:therapeutic use; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000803:Angiotensin I; D002216:Captopril; D001920:Bradykinin