Nitric oxide-angiotensin II interactions in angiotensin II-dependent hypertension

Many studies indicate that renal haemodynamic function in angiotensin II- ( ANG II) dependent hypertension is not reduced as much as would be predicted from the elevated ANG II levels suggesting that counteracting renoprotecti ve mechanisms are activated. One important renoprotective effect is mediate d by increased levels of nitric oxide. Recent studies using the ANG II-infu sed hypertensive rat model have shown that inhibition of nitric oxide synth esis (NOS) causes greater decreases in renal blood flow and glomerular filt ration rate in ANG II-infused hypertensive rats than in control rats. This augmented nitric oxide-dependent influence is localized primarily in the co rtex and to the preglomerular vasculature. The differential effects on the renal cortex and medulla are also reflected by the differences in NOS activ ities and protein expression. Ca2+-dependent NOS activity was significantly greater in the cortex but not the medulla of the ANG II-infused hypertensi ve rats compared with control rats. This was associated with marked activat ion of endothelial NOS protein levels and smaller increases in neuronal NOS protein levels in the cortex but not in the medulla. In contrast, the Ca2-independent NOS activity and the inducible NOS protein levels in the corte x were significantly lower in the ANG II-infused hypertensive rats. These d ata support the hypothesis that cortical Ca2+-dependent NOS, primarily endo thelial NOS, is stimulated during the early phases of ANG II-induced hypert ension and exerts a renoprotective effect on cortical haemodynamics.