Renal arteriolar contractile responses to angiotensin II in rats with poorly controlled diabetes mellitus.
1. Experiments were performed to test the hypothesis that renal arteriolar responses to angiotensin (Ang)II are altered in insulin-dependent diabetes mellitus. 2. Male Sprague-Dawley rats were treated with streptozotocin (STZ; 65 mg/kg, i.v.) or 0.9% NaCl vehicle (Sham). Partial insulin replacement maintained blood glucose levels at 422 +/- 6 mg/dL (STZ rats) for the ensuing 2 week period (86 +/- 4 mg/dL in Sham rats). The in vitro blood-perfused juxtamedullary nephron technique was used to study renal arteriolar diameter responses to exogenous AngII or K(+)-induced membrane depolarization. 3. Baseline afferent arteriolar diameter did not differ between kidneys harvested from Sham and STZ rats; however, constrictor responses to AngII were accentuated in kidneys from diabetic rats. During exposure to 10 nmol/L AngII, afferent diameter decreased by 37 +/- 5 and 18 +/- 4% in STZ and Sham kidneys, respectively. Efferent arterioles from Sham and STZ rats did not differ with regard to either baseline diameter or AngII responsiveness. 4. In experiments assessing afferent arteriolar responsiveness to membrane depolarization, 40 mmol/L K+ decreased lumen diameter by 73 +/- 11% in kidneys from Sham rats; however, the same depolarizing stimulus only reduced afferent diameter by 28 +/- 7% in STZ kidneys. 5. We conclude that afferent (but not efferent) arteriolar AngII responsiveness is increased during the early stages of poorly controlled diabetes mellitus in the rat. The exaggerated afferent arteriolar responsiveness to AngII occurs despite reduced sensitivity to membrane depolarization, suggesting that the emergence of alternative signalling processes or alterations in vasoactive modulator influences may underlie this phenomenon.
Carmines
P K
PK
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana, USA. pkcarmin@unmc.edu
Ohishi
K
K
D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D007606:Juxtaglomerular Apparatus / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D000809:Angiotensins; D011188:Potassium