Angiotensin II: enhanced renal responsiveness in young genetically hypertensive rats.
Renovascular and renal excretory responses to intrarenally infused angiotensin II (Ang II) (1 and 3 ng/min, one dose per rat) were assessed in young (approximately 6 weeks of age) anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats acutely treated with captopril. 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/min i.r.a.) significantly reduced renal blood flow (RBF) and increased renal vascular resistance (RVR) in SHR but not in WKY rats. At this dose, Ang II produced significant decreases in glomerular filtration rate (GFR), filtration fraction (FF), urine volume (UV) and urinary excretion of sodium (UNaV) and potassium (UkV) in SHR without altering any of these parameters in WKY rats. Ang II at either dose did not cause any increase in systemic blood pressure in either SHR or WKY rats. Ang II (3 ng/min i.r.a.) decreased RBF in both SHR and WKY rats to a similar extent. However, the higher dose of Ang II produced significant decrements 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 decreased 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 young SHR may be enhanced. The exaggerated renal reactivity to Ang II may be an important determinant of the development of hypertension in SHR.
Vyas
S J
SJ
Center for Clinical Pharmacology, University of Pittsburgh Medical Center, Pennsylvania, USA.
Jackson
E K
EK
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000235:genetics*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow / Q000187:drug effects
D000804:Angiotensin II; D000242:Cyclic AMP