Angiotensin II-induced renal vasoconstriction in genetic hypertension.
Previous studies demonstrate that renovascular responses to angiotensin II (Ang II) are enhanced in spontaneously hypertensive rats (SHRs); however, it is possible that this hyperresponsiveness is mediated by Ang II-induced release of substances from the adrenal gland. Previous studies also show that pertussis toxin normalizes renovascular responses to Ang II in SHRs; however, it is possible that this response is mediated by effects of pertussis toxin on endogenous Ang II levels and/or the sympathoadrenal axis. The purpose of this study was 2-fold: 1) to determine whether the renovascular response to Ang II in SHRs is enhanced even in adrenalectomized SHRs and 2) to determine whether pertussis toxin normalizes enhanced renovascular responses to Ang II when pertussis toxin-induced changes in the renin-angiotensin system and the sympathoadrenal axis are prevented. SHRs and Wistar Kyoto (WKY) rats were anesthetized and administered 20 ml/kg 0.9% saline, and an infusion of aldosterone and hydrocortisone was initiated. After bilateral adrenalectomy, left renal denervation, and pretreatment with captopril, animals received an intrarenal artery infusion of Ang II at 10 ng/kg/min for 5 min. Ang II-induced changes in renal vascular resistance were greater in SHRs compared with WKY rats (p =. 010, n = 19/group). Pertussis toxin (10 microgram/kg i.v. 3 days before the experiment) attenuated Ang II-induced changes in renal vascular resistance in SHR (p <.05), but not in WKY rats (strain x treatment interaction: p =.046). These results suggest that the enhanced renovascular response to Ang II in SHRs is mediated by a G(i)-dependent pathway within the renal vasculature.
Jackson
E K
EK
Department of Pharmacology, Center for Clinical Pharmacology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. edj+@pitt.edu
Herzer
W A
WA
Vyas
S J
SJ
Kost
C K
CK
D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000494:pharmacology; D004347:Drug Interactions; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D037342:Pertussis Toxin; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002395:Catecholamines; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D037342:Pertussis Toxin