TY - JOUR T1 - Low-Dose Angiotensin II Reduces Urinary Cyclic AMP Excretion in Spontaneously Hypertensive, But Not Normotensive, Rats: Independence from Hypertension and Renal Hemodynamic Effects of Angiotensin JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 115 LP - 123 VL - 291 IS - 1 AU - Edwin K. Jackson AU - William A. Herzer AU - Zaichuan Mi AU - Subhash J. Vyas AU - Curtis K. Kost, Jr Y1 - 1999/10/01 UR - http://jpet.aspetjournals.org/content/291/1/115.abstract N2 - The purpose of this study was to determine whether the greater inhibitory effect of angiotensin II (Ang II) on urinary cAMP excretion in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats is secondary to hypertension and/or renal hemodynamic changes induced by Ang II. SHRs and WKY rats were treated chronically from conception, 6 weeks of age, or 10 weeks of age (n = 8–10) with the angiotensin-converting enzyme inhibitor captopril (100 mg/kg/day). A fourth group was not treated chronically with captopril (n = 7). At ∼13 weeks of age, all rats were anesthetized, given a bolus of captopril (30 mg/kg), and received an intrarenal infusion of a low dose of Ang II (1 ng/min). SHRs compared with WKY rats were normotensive, mildly hypertensive, and moderately hypertensive when treated with captopril from conception, 6 weeks of age, and 10 weeks of age, respectively, whereas untreated SHRs were severely hypertensive. In SHRs, Ang II decreased urinary cAMP excretion (p < .001), and this effect was independent of duration of captopril pretreatment (p = .696). In WKY rats, Ang II did not affect urinary cAMP excretion. Low-dose Ang II caused small and similar changes in renal blood flow and glomerular filtration rate in SHRs versus WKY rats and did not affect urine volume in either strain. We conclude that the greater effect of Ang II on urinary cAMP excretion in SHRs is not due to hypertension or to the renal hemodynamic effects of Ang II, but most likely to a greater effect of Ang II on some compartment of renal adenylyl cyclase activity in SHRs. The American Society for Pharmacology and Experimental Therapeutics ER -