Adenosine regulates renal nitric oxide production in hypothyroid rats

In the hypothyroid kidney, exogenous adenosine (ADO) produces vasodilation and restores renal function to near-normal values. This study evaluates whe ther this response is mediated by nitric oxide synthesis stimulated by aden osine. GFR and urinary excretion of NO2-/NO3- (UNO2-/NO3-) were measured in normal (NL) and hypothyroid (HTX) rats under basal conditions and during i nfusion of: intra-aortic ADO, intravenously, 1,3-dipropyl-8p-sulfophenylxan thine (DPSPX), 8-cyclopentyl-1,3-dipropyl xanthine (DPCPX), N-omega-nitro-L -arginine methylester (L-NAME) + ADO, L-NAME + PSPX, L-NAME + DPCPX, and in trarenal (IR) ADO or DPCPX + IR ADO. Intra-aortic ADO induced a fall in GFR and increased UNO2-/NO3- slightly in NL rats; in HTX rats, both GFR and UN O2-/NO3- increased significantly. DPSPX and DPCPX in creased UNO2-/NO3- exc retion in NL animals with minor changes in GFR; the blockers increased both GFR and UNO2-/NO3- in HTX rats. L-NAME completely blocked the increase in NO2-/NO3- induced by ADO, DPSPX, and DPCPX. The intrarenal infusion of ADO at 1, 10, and 35 nmol/kg per mill progressively decreased GFR with a slight increase in UNO2-/ NO3 in NL rats; in the HTX, GFR increased with the high est dose and UNO2-/NO3- progressively increased. DPCPX prevented the fall i n GFR induced by intrarenal ADO in NL rats, with no further changes in UNO2 -/NO3- in HTX rats, intrarenal ADO under A1 blockade further increased GFR and UNO2/NO3. Arterial and venous ADO concentrations were lower in the HTX rats. In the HTX kidney, NO production was stimulated by ADO, most likely t hrough activation of A2 or A3 receptors, whereas A1 receptors had an inhibi tory effect. Thus, ADO receptors are involved in the regulation of kidney f unction in pathophysiologic conditions.