Increase in neurogenic nitric oxide metabolism by endothelin-1 in mesenteric arteries from hypertensive rats

We investigated, in mesenteric arteries from hypertensive rats (SHRs), the possible changes in neurogenic nitric oxide (NO) release produced by endoth elin-l (ET-I), and the mechanisms involved in this process. The contractile response induced by electrical field stimulation (EFS; 200 mA, 0.3 ms, 1-1 6 Hz, for 30 s) in deendotheliumized mesenteric segments was abolished by t etrodotoxin and phentolamine. The NO synthase inhibitor N-G-nitro-L-arginin e (L-NAME, 10 muM) increased the contractions caused by EFS. ET-I enhanced the contraction induced by EFS, which was unaltered by the subsequent addit ion of L-NAME. The ETA antagonist-receptor BQ-123 (1 muM) inhibited the eff ect of ET-1 on EFS response, whereas the ETB antagonist-receptor BQ-788 (3 muM) partially blocked it, and the subsequent addition of L-NAME restored t he contractile response in both cases. SOD (25 unit/ml) decreased the respo nse to EFS, and the subsequent addition of L-NAME increased this response. ET-I did not modify the decrease in EFS response induced by SOD, and the ad dition of L-NAME increased the response. None of these drugs altered the re sponse to exogenous noradrenaline (NA) or basal tone except SOD, which incr eased the basal tone, an effect blocked by phentolamine (1 muM). In arterie s preincubated with [H-3]NA, ET-1 did not modify the tritium efflux evoked by EFS, which was diminished by SOD. ET-I did not alter basal tritium efflu x, whereas SOD significantly increased the efflux. These results suggest th at EFS of SHR mesenteric arteries releases neurogenic NO, the metabolism of which is increased in the presence of ET-1 by the generation of superoxide anions.