ANGIOTENSIN-II - ENHANCED RENAL RESPONSIVENESS IN YOUNG GENETICALLY HYPERTENSIVE RATS

Renovascular and renal excretory responses to intrarenally infused ang iotensin II (Ang II) (1 and 3 ng/min, one dose per rat) were assessed in young (similar to 6 weeks of age) anesthetized spontaneously hypert ensive rats (SHR) and Wistar-Kyoto (WKY) rats acutely treated with cap topril. Urinary excretion of cyclic adenosine monophosphate (cAMP) was also measured in these rats to examine whether Ang II has an enhanced ability to inhibit adenylate cyclase activity in SHR. Ang II (1 ng/mi n i.r.a.) significantly reduced renal blood flow (RBF) and increased r enal vascular resistance (RVR) in SHR but not in WKY rats. At this dos e, Ang II produced significant decreases in glomerular filtration rate (GFR), filtration fraction (FF), urine volume (UV) and urinary excret ion of sodium (UNaV) and potassium (UKV) in SHR without altering any o f these parameters in WKY rats. Ang II at either dose did not cause an y increase in systemic blood pressure in either SHR or WKY rats. Ang I I (3 ng/min i.r.a.) decreased RBF in both SHR and WKY rats to a simila r extent. However, the higher dose of Ang II produced significant decr ements in GFR, FF, UV, UNaV and fractional excretion of sodium in SHR but not in WKY rats. Also, Ang II at both the doses significantly decr eased urinary cAMP excretion rate in SHR without affecting the same in WKY rats. These data demonstrate that, even during the developmental phase of hypertension, the SHR kidney is more responsive to Ang II as compared with the WKY rat kidney. Also, these results suggest that the ability of Ang II to inhibit renal adenylate cyclase activity in youn g SHR may be enhanced. The exaggerated renal reactivity to Ang II may be an important determinant of the development of hypertension in SHR.