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 per iod (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 har vested from Sham and STZ rats; however, constrictor responses to AngII were accentuated in kidneys from diabetic rats. During exposure to 10 nmol/L. A ngII, afferent diameter decreased by 37+/-5 and 18+/-4% in STZ and Sham kid neys, respectively. Efferent arterioles from Sham and STZ rats did not diff er 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 kidney s from Sham rats; however er, the same depolarizing stimulus only reduced a fferent diameter by 28+/-7% in STZ kidneys. 5, We conclude that afferent (hut not efferent) arteriolar AngII responsive ness is increased during the early stages of poorly controlled diabetes mel litus in the rat. The exaggerated afferent arteriolar responsiveness to Ang II occurs despite reduced sensitivity to membrane depolarization, suggestin g that the emergence of alternative signalling processes or alterations in vasoactive modulator influences mag underlie this phenomenon.