Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats

Francisco M. Ruiz-Marcos, M. Clara Ortiíz, Lourdes A. Fortepiani, Francisco J.A. Nadal, Noemií M. Atucha, Joaquiín Garciía-Estañ

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26 Scopus citations

Abstract

In the present study we analyzed mesenteric vascular reactivity of chronic nitric oxide (NO)-deficient hypertensive rats (NW-nitro-L-Arginine Methyl Ester, L-NAME, 50 mg/kg/day, oral, 3 weeks). Perfusion pressure changes in response to cumulative additions of methoxamine and KCl were significantly increased in the mesenteric vessels of the L-NAME-treated as compared with vessels of the controls. Verapamil reduced the responses to methoxamine, but those of the hypertensive rats were still enhanced. In contrast, responses to KCl were almost completely abolished by verapamil. In mesenteric vessels perfused with zero calcium and high-potassium Krebs, pressor responses to the re-addition of calcium were also significantly enhanced in the hypertensive rats compared to the controls. Vasodilator responses to acetylcholine in KCl-preconstricted vessels, while still significant, were reduced in the L-NAME-treated rats. In this case, acute inhibition of NO blocked the vasodilator responses to acetylcholine and abolished the differences between the two groups. In methoxamine-preconstricted vessels and in the presence of acute inhibition of NO and prostaglandins, vasodilator responses to acetylcholine were significantly greater in the hypertensive vessels than in controls. In conclusion, the mesenteric vessels of L-NAME hypertensive rats show an enhanced response to vasopressors which is related to calcium entry. These data also reveal the existence of an enhanced role of a NO and prostaglandin-independent vasodilator factor, probably endothelium-derived hyperpolarizing factor that may play a compensatory role in the deficiency of NO.

Original languageEnglish (US)
Pages (from-to)273-279
Number of pages7
JournalEuropean Journal of Pharmacology
Volume412
Issue number3
DOIs
StatePublished - Feb 2 2001
Externally publishedYes

Keywords

  • Acetylcholine
  • Arterial hypertension
  • EDHF (endothelium-dependent hyperpolarizing factor)
  • Methoxamine
  • Nitric oxide (NO)
  • Vascular reactivity

ASJC Scopus subject areas

  • Pharmacology

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