Interactions Between Nitric Oxide and Angiotensin II on Renal Cortical and Papillary Blood Flow

Abstract

This study examined the role of angiotensin II (Ang II) on the effects of nitric oxide (NO) synthesis blockade on renal cortical and papillary blood flow in innervated and denervated kidneys of volume-expanded Munich-Wistar rats with hormonal influences on the kidney that were held constant by intravenous infusion. Cortical (CBF) and papillary (PBF) blood flow were measured by laser-Doppler flowmetry. A low dose of N omega-nitro-L-arginine methyl ester (L-NAME, 3.7 nmol x kg[-1] x min[-1]) reduced CBF only in innervated kidneys, and this effect was abolished by subsequent administration of valsartan (an AT1 antagonist). L-NAME 3.7 nmol x kg(-1) x min(-1) improved PBF autoregulation by lowering PBF to the range of 100 to 140 mm Hg of perfusion pressure, and this effect was attenuated or abolished by valsartan in innervated and denervated kidneys, respectively. These results indicate that the cortical and medullary vasoconstriction induced by a low dose of L-NAME are caused by potentiation of the vasoconstrictor influence of renal sympathetic nerves and Ang II. A higher dose of L-NAME (37 nmol x kg[-1] x min[-1]) lowered CBF and PBF in both innervated and denervated kidneys. This effect of L-NAME on the cortical circulation was abolished by valsartan, but this AT1 antagonist had no effect on the medullary vasoconstriction produced by NO synthesis blockade. Therefore, a higher dose of L-NAME induces a renal cortical vasoconstriction through potentiation of the renin-angiotensin system, whereas the fall of PBF seen after L-NAME 37 nmol x kg(-1) x min(-1) seems to be caused primarily by NO suppression. This Ang II potentiation produced by L-NAME in the renal cortex seems to be mediated by AT1 receptors, because it was unaffected by PD123319 (an AT2 antagonist). The results of the present study indicate that NO is an important modulator of the vasoconstrictor influence of Ang II in the renal cortical circulation of the rat. However, although there are some interactions between NO and renal nerves and Ang II on the medullary circulation, the renal medullary vasoconstriction produced by L-NAME appears to be caused primarily by NO suppression, with little influence of the renal vasoconstrictor systems.