A NEUROMODULATORY ROLE FOR NEURONAL NITRIC-OXIDE IN THE RABBIT RENAL-ARTERY

1 The effects of the nitric oxide synthase inhibitor N-G-nitro-L-argin ine methyl ester (L-NAME) on vasoconstrictor responses to transmural e lectrical nerve stimulation and noradrenaline were examined in the rab bit isolated renal artery with and without an intact endothelium. In a ddition, the effect of removing the endothelium from the renal artery on vasoconstrictor responses to transmural electrical nerve stimulatio n and noradrenaline was also investigated. Immunohistofluorescence tec hniques were carried out to determine if there were any nitrergic nerv es supplying the renal artery. 2 The vasoconstriction produced in resp onse to transmural electrical nerve stimulation (2-64 Hz) was signific antly enhanced in the presence of L-NAME (3 x 10(-6), 10(-5), 3 x 10(- 5) and 10(-4) M). 3 L-NAME (3 x 10(-6), 10(-5), 3 x 10(-5) and 10(-4) M) did not significantly affect the maximum vasoconstriction produced in response to noradrenaline. However, the noradrenaline dose-response curve was significantly shifted to the left by the addition of L-NAME (3 x 10(-6), 10(-5), 3 x 10(-5) and 10(-4) M). 4 The increase in the amplitude of the vasoconstriction, produced in response to transmural electrical nerve stimulation (16 Hz) and noradrenaline (10(-5) M) in t he presence of L-NAME (10(-5) M) was not observed when L-arginine (10( -3) M) was added in addition to L-NAME (10(-5) M). 5 Removing the endo thelium did not significantly affect the response to transmural electr ical nerve stimulation (1-64 Hz). The maximum vasoconstriction in resp onse to noradrenaline was also unaffected by the removal of the endoth elium. The pD(2) value for noradrenaline obtained from vessels with no endothelium was significantly greater than the pD(2) value obtained f rom vessels with an intact endothelium (5.90+/-0.11 and 5.16+/-0.03, r espectively). 6 On renal artery segments with no endothelium L-NAME (3 x 10(-5) M) significantly enhanced the response to transmural electri cal nerve stimulation (2-64 Hz). L-NAME did not affect the maximum res ponse to noradrenaline. However, there was a significant shift to the right of the noradrenaline dose-response curve in the presence of L-NA ME (3 x 10(-5) M). 7 Both nitric oxide synthase-containing and NADPH-d iaphorase stained nerves were located on the adventitial-medial border of the rabbit renal artery. 8 The present study has suggested a presy naptic inhibitory action for nitric oxide (probably derived from ident ified perivascular nitrergic nerves), on perivascular sympathetic vaso constrictor nerve mediated responses of the rabbit renal artery. In co ntrast, the enhancement of the response to noradrenaline by L-NAME can be attributed to inhibition of the synthesis of endothelium-derived n itric oxide.