In rats with streptozotocin (STZ)-induced diabetes, the renal vasoconstrictor effect of adenosine is enhanced. We investigated the role of nitric oxide (NO) in the renal vascular response to exogenous and endogenous adenosine in control and STZ diabetic rats. Exogenous adenosine (0.01-100 nmol) injected into the abdominal aorta decreased renal blood flow (RBF) in a dose-dependent manner to a much greater extent in STZ rats than in control rats (P < 0.001). Inhibition of NO synthesis with N-nitro-L-arginine (L-NNA, 30 µmol/kg iv) and with renal perfusion pressure controlled potentiated the adenosine-induced renal vasoconstriction to a significantly greater extent in control rats than in STZ rats. In control rats, L-NNA shifted the dose-response curve of exogenous adenosine-induced RBF reductions to the left by a factor of 32 [half-maximal effective dose (ED₅₀), from 5.5 to 0.17 nmol adenosine, n = 6] and in STZ rats only by a factor of 4.6 (ED₅₀, from 0.32 to 0.07 nmol adenosine, n = 6). The renal response to endogenous adenosine was assessed by the magnitude of the postocclusive reduction of RBF (POR) after a 30-s renal artery occlusion. POR was markedly enhanced in STZ rats (67.8 ± 3.8%, P < 0.001) compared with control rats (38.8 ± 4.3%). L-NNA markedly enhanced POR in control rats but did not increase POR in STZ rats. These findings demonstrate a greater potentiation of the adenosine-induced renal vasoconstriction in the presence of L-NNA infusion in control rats compared with STZ rats. We conclude that the increased vasoconstrictor sensitivity of the diabetic renal vasculature to adenosine is caused by a defective NO-dependent renal vasodilation of the afferent arteriole in diabetic rats.

renal hemodynamics; experimental insulin-dependent diabetes mellitus; nitric oxide-dependent renal vasodilation; diabetic dysfunctional vasoregulation; renal ischemia

This article has been cited by other articles:

				T. D. Bell, G. F. DiBona, R. Biemiller, and M. W. Brands Continuously measured renal blood flow does not increase in diabetes if nitric oxide synthesis is blocked Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1449 - F1456. [Abstract] [Full Text] [PDF]

				V. Vallon, B. Muhlbauer, and H. Osswald Adenosine and kidney function. Physiol Rev, July 1, 2006; 86(3): 901 - 940. [Abstract] [Full Text] [PDF]

				G. Zhao, A. Linke, X. Xu, M. Ochoa, F. Belloni, L. Belardinelli, and T. H. Hintze Comparative Profile of Vasodilation by CVT-3146, a Novel A2A Receptor Agonist, and Adenosine in Conscious Dogs J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 182 - 189. [Abstract] [Full Text] [PDF]

				P. B. Hansen and J. Schnermann Vasoconstrictor and vasodilator effects of adenosine in the kidney Am J Physiol Renal Physiol, October 1, 2003; 285(4): F590 - F599. [Abstract] [Full Text] [PDF]

				T. Wronski, E. Seeliger, P. B. Persson, C. Forner, C. Fichtner, J. Scheller, and B. Flemming The step response: a method to characterize mechanisms of renal blood flow autoregulation Am J Physiol Renal Physiol, October 1, 2003; 285(4): F758 - F764. [Abstract] [Full Text] [PDF]

				R. Komers and S. Anderson Paradoxes of nitric oxide in the diabetic kidney Am J Physiol Renal Physiol, June 1, 2003; 284(6): F1121 - F1137. [Abstract] [Full Text] [PDF]

				Y.-F. Chen, P.-L. Li, and A.-P. Zou Oxidative stress enhances the production and actions of adenosine in the kidney Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2001; 281(6): R1808 - R1816. [Abstract] [Full Text] [PDF]

				B. FLEMMING, N. ARENZ, E. SEELIGER, T. WRONSKI, K. STEER, and P. B. PERSSON Time-Dependent Autoregulation of Renal Blood Flow in Conscious Rats J. Am. Soc. Nephrol., November 1, 2001; 12(11): 2253 - 2262. [Abstract] [Full Text] [PDF]

				N. ISHII, K. P. PATEL, P. H. LANE, T. TAYLOR, K. BIAN, F. MURAD, J. S. POLLOCK, and P. K. CARMINES Nitric Oxide Synthesis and Oxidative Stress in the Renal Cortex of Rats with Diabetes Mellitus J. Am. Soc. Nephrol., August 1, 2001; 12(8): 1630 - 1639. [Abstract] [Full Text] [PDF]

				S. M. Fitzgerald and M. W. Brands Nitric oxide may be required to prevent hypertension at the onset of diabetes Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E762 - E768. [Abstract] [Full Text] [PDF]

				R. Komers, J. N. Lindsley, T. T. Oyama, K. M. Allison, and S. Anderson Role of neuronal nitric oxide synthase (NOS1) in the pathogenesis of renal hemodynamic changes in diabetes Am J Physiol Renal Physiol, September 1, 2000; 279(3): F573 - F583. [Abstract] [Full Text] [PDF]

				Y. Ding, N. D. Vaziri, R. Coulson, V. S. Kamanna, and D. D. Roh Effects of simulated hyperglycemia, insulin, and glucagon on endothelial nitric oxide synthase expression Am J Physiol Endocrinol Metab, July 1, 2000; 279(1): E11 - E17. [Abstract] [Full Text] [PDF]

				G. C. Schoonmaker, R. W. Fallet, and P. K. Carmines Superoxide anion curbs nitric oxide modulation of afferent arteriolar ANG II responsiveness in diabetes mellitus Am J Physiol Renal Physiol, February 1, 2000; 278(2): F302 - F309. [Abstract] [Full Text] [PDF]

				A. C. Pflueger, T. S. Larson, S. Hagl, and F. G. Knox Role of nitric oxide in intrarenal hemodynamics in experimental diabetes mellitus in rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1999; 277(3): R725 - R733. [Abstract] [Full Text] [PDF]

				S. M. Fitzgerald and M. W. Brands Hypertension in L-NAME-treated diabetic rats depends on an intact sympathetic nervous system Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1070 - R1076. [Abstract] [Full Text] [PDF]