Nonendothelial NO blunts sympathetic response of normotensive rats but not of SHR.

The inhibitory role of NO on sympathetic-induced contraction of resistance vessels of spontaneously hypertensive rats (SHR) has not been defined. Accordingly, we investigated the effect of endothelial removal or NO synthase inhibition on vasoconstrictor responses to sympathetic stimulation or phenylephrine in perfused mesenteric beds isolated from normotensive rats (NR) and SHR. Electrical stimulation (10 to 64 Hz) of perivascular nerves elicited a frequency-dependent increase in perfusion pressure that was greater in preparations from SHR (maximal effect: 223.4+/-8.4 versus 117.6+/-10.3 mm Hg in NR, n=6, P<0.001), and endothelium removal did not affect these responses in arteries from NR but caused a significant shift to the left of the frequency-response curve in arteries from SHR. In arteries with endothelium, inhibition of NO synthase with N(G)-nitro-L-arginine (L-NNA, 50 micromol/L) augmented the vasoconstrictor responses to sympathetic stimulation in both NR and SHR preparations. In preparations that had the endothelium removed, however, L-NNA potentiated only the responses to sympathetic stimulation of NR arteries. Vasoconstrictor responses to phenylephrine was potentiated by endothelium removal and in the presence of L-NNA only when the endothelium was intact in both NR and SHR arteries. The number of NADPH-diaphorase-positive cells in the superior mesenteric sympathetic ganglion of SHR was significantly less compared with that of NR. In conclusion, these data suggest a prejunctional inhibitory action of non-endothelial-derived NO, most probably neuronal-derived NO, on sympathetic-mediated vasoconstriction in NR arteries. In contrast, enhancement of the sympathetic-mediated vasoconstriction in SHR arteries elicited by L-NNA can be attributed to inhibition of endothelial-derived NO.