Inhibition of vascular nitric oxide-cGMP pathway by plasma from ischemic hindlimb of rats

J. S. Jin, R Clinton Webb, L. G. D'Alecy

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The hypothesis was tested that plasma from ischemic hindlimbs facilitates hypertension. Ischemia-induced hypertension was generated in rats by infrarenal aortic cross clamping for 5 h after which plasma was obtained from femoral vein blood. In vitro contractile activity of naive aortic rings incubated for 2 h in plasma collected from ischemic rats demonstrated reduced relaxation to acetylcholine and nitroglycerin. Methylene blue (10-5 M) induced greater contraction in rings incubated in control vs. ischemic plasma, suggesting that endogenous guanylate cyclase activity is decreased by ischemic plasma. However, 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP) relaxed equally strips incubated in ischemic or control plasma. Acetylcholine-induced nitrite release was significantly lower in ischemic vs. control plasma-incubated strips (8.6 ± 2.7 vs. 28.2 ± 2.3 ng/10 mg tissue wt, respectively). The impaired relaxation to acetylcholine in ischemic plasma-incubated rings was significantly increased by L-arginine but not by prior treatment of ischemic plasma with heating or superoxide dismutase and catalase. These findings suggest the impaired relaxation is mediated through inhibition of the nitric oxide-cGMP pathway. Prolonged blunting of vasodilation by ischemic plasma may therefore contribute to maintenance of a sustained vasoconstriction and ischemic hypertension.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume269
Issue number1 38-1
StatePublished - Jan 1 1995

Keywords

  • 8-bromoguanosine 3',5'- cyclic monophosphate
  • acetylcholine
  • aortic surgery
  • intermittent claudication
  • methylene blue
  • nitrite
  • nitroglycerin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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