title: Increase in neurogenic nitric oxide metabolism by endothelin-1 in mesenteric arteries from hypertensive rats.
abstract: We investigated, in mesenteric arteries from hypertensive rats (SHRs), the possible changes in neurogenic nitric oxide (NO) release produced by endothelin-1 (ET-1), and the mechanisms involved in this process. The contractile response induced by electrical field stimulation (EFS; 200 mA, 0.3 ms, 1-16 Hz, for 30 s) in deendotheliumized mesenteric segments was abolished by tetrodotoxin and phentolamine. The NO synthase inhibitor N(G)-nitro-L-arginine (L-NAME, 10 microM) increased the contractions caused by EFS. ET-1 enhanced the contraction induced by EFS, which was unaltered by the subsequent addition of L-NAME. The ETA antagonist-receptor BQ-123 (1 microM) inhibited the effect of ET-1 on EFS response, whereas the ETB antagonist-receptor BQ-788 (3 microM) partially blocked it, and the subsequent addition of L-NAME restored the contractile response in both cases. SOD (25 unit/ml) decreased the response to EFS, and the subsequent addition of L-NAME increased this response. ET-1 did not modify the decrease in EFS response induced by SOD, and the addition of L-NAME increased the response. None of these drugs altered the response to exogenous noradrenaline (NA) or basal tone except SOD, which increased the basal tone, an effect blocked by phentolamine (1 microM). In arteries preincubated with [3H]NA, ET-1 did not modify the tritium efflux evoked by EFS, which was diminished by SOD. ET-1 did not alter basal tritium efflux, whereas SOD significantly increased the efflux. These results suggest that 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.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ferrer
authors.forename: M J
authors.initials: MJ
authors.lastname: Alonso
authors.forename: M
authors.initials: M
authors.lastname: Salaices
authors.forename: J
authors.initials: J
authors.lastname: Marín
authors.forename: G
authors.initials: G
authors.lastname: Balfagón
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004558:Electric Stimulation; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008638:Mesenteric Arteries; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D014665:Vasodilator Agents; D009569:Nitric Oxide; C086539:BQ 788; D013482:Superoxide Dismutase; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester