Reversal of glibenclamide-induced coronary vasoconstriction by enhanced perfusion pulsatility: Possible role for nitric oxide

Pasquale Pagliaro, Nazareno Paolocci, Takayoshi Isoda, Walter F. Saavedra, Genshiro Sunagawa, David A Kass

Research output: Contribution to journalArticle

Abstract

Objectives: ATP-sensitive potassium channels (K+(ATP)) prominently contribute to basal coronary tone; however, flow reserve during exercise remains unchanged despite channel blockade with glibenclamide (GLI). We hypothesized that increasing perfusion pulsatility, as accompanies exercise, offsets vasoconstriction from K+(ATP)-channel blockade, and that this effect is blunted by nitric oxide synthase (NOS) inhibition. Methods: In 31 anaesthetized dogs the left anterior descending artery was blood-perfused by computer-controlled servo-pump, with real-time arterial perfusion pulse pressure (PP) varied from 40 and 100 mm Hg at a constant mean pressure and cardiac workload. Results: At control PP (40 mm Hg), GLI (50 μg/min/kg, i.c.) lowered mean regional coronary flow from 37±5 to 25±4 ml/min (P+ blockade by likely enhancing NO release. This mechanism may assist exercise-mediated dilation in settings where K(ATP)/+ opening is partially compromised. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)1001-1009
Number of pages9
JournalCardiovascular Research
Volume45
Issue number4
DOIs
StatePublished - Mar 2000

Fingerprint

Glyburide
Vasoconstriction
Nitric Oxide
Perfusion
Adenosine Triphosphate
Blood Pressure
KATP Channels
Workload
Nitric Oxide Synthase
Dilatation
Arteries
Dogs
Pressure

Keywords

  • Blood pressure
  • Coronary circulation
  • K-ATP channels
  • Nitric oxide
  • Vasoconstriction/vasodilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Reversal of glibenclamide-induced coronary vasoconstriction by enhanced perfusion pulsatility : Possible role for nitric oxide. / Pagliaro, Pasquale; Paolocci, Nazareno; Isoda, Takayoshi; Saavedra, Walter F.; Sunagawa, Genshiro; Kass, David A.

In: Cardiovascular Research, Vol. 45, No. 4, 03.2000, p. 1001-1009.

Research output: Contribution to journalArticle

Pagliaro, Pasquale ; Paolocci, Nazareno ; Isoda, Takayoshi ; Saavedra, Walter F. ; Sunagawa, Genshiro ; Kass, David A. / Reversal of glibenclamide-induced coronary vasoconstriction by enhanced perfusion pulsatility : Possible role for nitric oxide. In: Cardiovascular Research. 2000 ; Vol. 45, No. 4. pp. 1001-1009.
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