Endothelium-dependent responses of cerebral blood vessels during chronic hypertension

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

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 μm) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3×10-7 M) dilated pial arterioles by 35±6% (mean±SEM) in WKY rats, but only 21±3% in SHRSP (p<0.05 versus WKY rats). Both nitric oxide (5×10-7 M) and nitroglycerin (10-5 M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10-5 M) produced more vasodilatation in WKY rats than in SHRSP (32±8% versus 9±4%, p<0.05). Responses to A23187 (10-5 M) were inhibited by indomethacin (46±13% versus 15±5%, p<0.05) in WKY rats, whereas responses to A23187 (10-6 M) were potentiated modestly by indomethacin (-3±2% versus 4±2%, p<0.05) in SHRSP. Thus, 1) chronic hypertension impairs responses to two distinct endothelium-dependent dilators in pial arterioles, 2) responses of pial arterioles to nitric oxide are not altered during chronic hypertension, 3) impairment of endothelium-dependent responses in chronic hypertension involves an alteration in postreceptor mechanisms, and 4) impaired responses to A23187 in chronic hypertension may be due in part to co-release of a constrictor substance through the cyclooxygenase pathway.

Original languageEnglish (US)
Pages (from-to)612-618
Number of pages7
JournalHypertension
Volume17
Issue number5
DOIs
StatePublished - May 1991

Keywords

  • Arterioles
  • Bradykinin
  • Endothelium
  • Glyceryl trinitrate
  • Nitric oxide
  • Stroke-prone spontaneously hypertensive rats

ASJC Scopus subject areas

  • Internal Medicine

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