Mechanisms of impaired endothelium-dependent cerebral vasodilatation in response to bradykinin in hypertensive rats

Shuh Tsong Yang, William G. Mayhan, Frank M. Faraci, Donald D. Heistad

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Abstract

Bradykinin produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats than in nonnotensive Wistar-Kyoto rats. The goals of this study were to determine the mediator of bradykinin-induced dilatation in cerebral arterioles of rats and to determine whether responses to this mediator are altered in hypertensive rats. Diameter of pial arterioles (20-65 µm) was measured using intravital microscopy in 18 nonnotensive and 17 hypertensive rats. Superfusion of 3×10−7 M bradykinin dilated pial arterioles by 53±4% (mean±SEM) in nonnotensive rats but only 33±6% in hypertensive rats (p<0.05 versus nonnotensive rats). Vasodilatation in response to bradykinin was almost completely inhibited by 280 units/ml catalase in both nonnotensive and hypertensive rats (n=l and n=l, respectively) whereas 150 units/ml superoxide dismutase (n= 6 and n=5, respectively) and 1 mM deferoxamine (n=5 and n=5, respectively) did not attenuate bradykinin-induced vasodilatation. These findings suggest that hydrogen peroxide is the mediator of bradykinin-induced dilatation in cerebral arterioles of rats. We also examined responses of cerebral arterioles to hydrogen peroxide in five nonnotensive and six hypertensive rats. Dilator responses of cerebral arterioles to 3.2 × 10−5 M to 1.6×10−4 M hydrogen peroxide did not differ in nonnotensive and hypertensive rats, which suggests that impaired dilatation of cerebral arterioles in response to bradykinin is not related to altered responsiveness of smooth muscle to an endothelium-derived relaxing factor. In summary, our findings suggest that hydrogen peroxide mediates bradykinin-induced cerebral vasodilatation in rats and that impaired cerebral vasodilatation in response to bradykinin during chronic hypertension is not due to altered responsiveness of smooth muscle to hydrogen peroxide.

Original languageEnglish (US)
Pages (from-to)1177-1182
Number of pages6
JournalStroke
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 1991

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Keywords

  • Bradykinin
  • Free radicals
  • Hydrogen peroxide
  • Rats

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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