Altered vascular reactivity in mice made hypertensive by nitric oxide synthase inhibition

A. Elizabeth Linder, David S. Weber, Steven E. Whitesall, Louis G. D'Alecy, R Clinton Webb

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

This study tested the hypothesis that nitric oxide (NO) synthase inhibition in mice would result in hypertension characterized by increased agonist-induced vasoconstrictor responsiveness and attenuated endothelium-dependent vasodilation. Administration of N ω -nitro-L-arginine (L-NNA), an NO synthase inhibitor (1 g/L, 4 weeks), via drinking water to mice resulted in significant elevations in blood pressure. Phenylephrine-induced contraction was significantly increased in aortic rings from L-NNA-treated mice compared with rings from control mice. Aortic rings from control mice showed a concentration-dependent relaxation to acetylcholine whereas those obtained from L-NNA-treated mice showed a biphasic response, contracting at lower concentrations while relaxing at higher concentrations. Aortic rings from L-NNA-treated mice had decreased relaxation to acetylcholine and increased sensitivity to sodium nitroprusside compared with control rings. The relaxation induced by an NO-independent soluble guanylyl cyclase activator was not different between groups. In aortic rings from control and L-NNA-treated mice pre-contracted with phenylephrine, the administration of L-NNA to the organ bath caused additional and sustained contraction. When compared with the contraction induced by phenylephrine, L-NNA-induced contraction in aorta from control mice was significantly higher than that in aorta from L-NNA-treated mice. We conclude that mice treated with L-NNA develop hypertension and that a reduction in NO availability is responsible for the changes observed in vascular reactivity.

Original languageEnglish (US)
Pages (from-to)438-444
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume46
Issue number4
DOIs
StatePublished - Oct 1 2005

Keywords

  • Hypertension
  • Mice
  • Nitric oxide
  • Nitric oxide synthase
  • Vascular reactivity

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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