Defective modulation of angiotensin II-induced renal vasoconstriction in hypertensive rats.
In a previous study we observed that the ability of intravenous infusions of prostaglandin I2 to attenuate vasoconstriction caused by intravenous infusions of angiotensin II was reduced in the renal but not mesenteric vasculature of spontaneously hypertensive rats (SHR). One objective of the current study was to determine whether a renal defect in the angiotensin II/prostaglandin I2 interaction in SHR could be confirmed even when confounding hemodynamic changes induced by intravenous infusions of prostaglandin I2 were avoided. The second objective was to determine whether abnormal modulation of angiotensin II-induced renal vasoconstriction was present even in SHR that were maintained normotensive from an early age. Four-week-old SHR and normotensive Wistar-Kyoto rats were randomized to receive either normal drinking water or drinking water containing captopril (100 mg/kg per day). At 14 to 18 weeks of age, rats were pretreated with indomethacin to block the production of endogenous prostaglandin I2, and changes in mesenteric and renal vascular resistances induced by suprarenal/supramesenteric aortic infusions of angiotensin II (10, 30, and 100 ng/kg per minute) were elicited in the presence and absence of aortic infusions of prostaglandin I2 (0.1 and 0.3 micrograms/kg per minute). Data were analyzed globally using four- and three-factor ANOVAs. The ability of prostaglandin I2 to attenuate the renal vasoconstrictor response to angiotensin II was strain specific (P = .0138), and this strain-specific interaction was not influenced by chronic treatment with captopril (P = .3526).(ABSTRACT TRUNCATED AT 250 WORDS)
Jackson
E K
EK
Center for Clinical Pharmacology, University of Pittsburgh Medical Center, PA 15261.
Herzer
W A
WA
D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D011464:Epoprostenol / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*
D000804:Angiotensin II; D011464:Epoprostenol