Interactions of cAMP-mediated vasodilators with angiotensin II in rat kidney during hypertension.
In previous studies [C. Chatziantoniou and W.J. Arendshorst. Am. J. Physiol. 263 (Renal Fluid Electrolyte Physiol. 32): F573-F580, 1992], we reported that vasodilator prostaglandins (PGs) are defective in buffering the angiotensin II (ANG II)-induced vasoconstriction in the renal vasculature of spontaneously hypertensive rats (SHR). The purpose of the present study was to determine whether this defect in SHR kidneys is specific to PGs or generalized to the action of vasodilators and to gain insight into which intracellular signal(s) mediates this abnormality. Renal blood flow (RBF; electromagnetic flowmetry) was measured in 7 wk-old anesthetized, euvolemic SHR and normotensive Wistar-Kyoto (WKY) rats pretreated with indomethacin to avoid interactions with endogenous PGs. ANG II (2 ng) was injected into the renal artery before and during continuous intrarenal infusion of fenoldopam [DA1 receptor agonist and G protein-dependent stimulator of adenosine 3',5'-cyclic monophosphate (cAMP)], forskolin (G protein-independent stimulator of cAMP), dibutyryl-cAMP (soluble cAMP), and acetylcholine (cGMP stimulator). Each vasodilator was infused at a low dose that did not affect baseline arterial pressure or RBF. In the control period, ANG II reduced RBF by 50% in both strains. Infusion of fenoldopam significantly blunted the ANG II-induced vasoconstriction in WKY, but not in SHR. In contrast, forskolin, dibutyryl-cAMP, and acetylcholine effectively buffered the vasoconstriction due to ANG II in both SHR and WKY. These results suggest that renal vasodilators acting through receptor binding to stimulate the cAMP signaling pathway are ineffective in counteracting the ANG II-induced vasoconstriction in SHR kidneys. (ABSTRACT TRUNCATED AT 250 WORDS)
Chatziantoniou
C
C
Department of Physiology, University of North Carolina at Chapel Hill 27599-7545.
Ruan
X
X
Arendshorst
W J
WJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D055590:Electromagnetic Phenomena; D018818:Fenoldopam; D006973:Hypertension / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects*; D012212:Rheology; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D000804:Angiotensin II; D003994:Bucladesine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D018818:Fenoldopam; D000109:Acetylcholine