Hagl, Siegfried

The role of nitric oxide (NO) in the regulation of the intrarenal microcirculation in streptozotocin (STZ)-induced diabetes mellitus in rats is not clear. We examined renal cortical and papillary hemodynamics in STZ rats and determined the effects of systemic inhibition and stimulation of NO synthesis. Renal blood flow in cortical (QCC), and inner medullary ascending (QAV) and descending (QDV) vasa recta capillaries was measured by fluorescence videomicroscopy in STZ Munich-Wistar rats and nondiabetic control rats. Ten days after STZ injection (80 mg/kg ip), basal QCCand QDVwere significantly greater in STZ rats ( n = 16) compared with control rats ( n = 15). Infusion of NG-monomethyl-l-arginine (l-NMMA, 15 mg/kg bolus, 500 μg ⋅ min−1⋅ kg−1iv) decreased QCC(−41%), QAV(−38%), and QDV(−37%) in control rats ( n = 6) and to a significantly greater magnitude than in STZ rats ( n = 7), QCC(−14%), QAV(−20%), and QDV(−25%). Coinfusion ofl-arginine (l-Arg, 1 mg ⋅ kg−1⋅ min−1iv) with l-NMMA increased QCCto a significantly greater extent ( P < 0.01) in control rats compared with STZ rats. In subsequent studies, infusion ofl-Arg alone increased QCC(+50%), QAV(+16%), and QDV(+11%) in control rats ( n = 5) but had no effect in STZ rats ( n = 5). These results show that the response of renal cortical and papillary capillary blood flow to both inhibition and stimulation of NO synthesis is attenuated in the early onset of STZ-diabetes mellitus rats compared with control rats.