Vascular reactivity to angiotensin II in blood-perfused kidneys of hypertensive diabetic rats.
The present study examined vascular reactivity to angiotensin II in blood-perfused kidneys of diabetic normotensive Wistar-Kyoto (WKY) and diabetic spontaneously hypertensive rats (SHR). In addition, the effect of the angiotensin AT1 receptor antagonist, CV-11974 (2-ethoxy-l-[[2'-(1 H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1 H-benzimidazole-7-carboxylic acid), on angiotensin II responses was examined. Dose-response curves to angiotensin II (0.1-30 micrograms/kg, i.a.) were obtained in kidneys of control- and diabetic-WKY rats and -SHR rats, either in the absence or presence of CV-11974 (3 micrograms/kg, i.v.). In all four treatment groups, angiotensin II produced dose-dependent increases in renal perfusion pressure with the order or reactivity: control-SHR > control-WKY = diabetic-SHR > diabetic-WKY. In the presence of CV-11974 (3 micrograms/kg, i.v.), dose-response curves to angiotensin II were significantly inhibited in kidneys of control-SHR and -WKY rats. However, CV-11974 (3 micrograms/kg, i.v.) had no significant effect on angiotensin II responses in kidneys of diabetic-SHR or -WKY rats. These results suggest that diabetes in normotensive rats is associated with impaired renal responsiveness to angiotensin II, while hypertension augments renal responsiveness to angiotensin II. However, the combination of diabetes and hypertension has largely offset the opposite effects on angiotensin II responses seen separately. Importantly, the lack of effect of CV-11974 in diabetic rats, with or without hypertension, has been identified. While the reasons for these alterations have yet to be determined, they may involve changes in angiotensin II receptor mechanisms (e.g. density and/or affinity).
Farina
N K
NK
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Hodgson
W C
WC
Widdop
R E
RE
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D006973:Hypertension / Q000150:complications*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000804:Angiotensin II