Acute endothelin-receptor inhibition does not attenuate acetylcholine-induced coronary vasoconstriction in experimental hypercholesterolemia

Arteriosclerosis, Thrombosis, and Vascular Biology
D HasdaiA Lerman

Abstract

Endothelin (ET) may mediate the enhanced coronary vasoconstriction associated with hypercholesterolemia. We hypothesized that short-term inhibition of ET receptors attenuates the coronary epicardial vasoconstrictor response to acetylcholine in experimental hypercholesterolemia. ET-1 (group I, n=5; 5 ng x kg[-1] x min[-1]) and acetylcholine (group III, n=7; 10[-6] to 10[-4] mol/L) were given by intracoronary infusion in pigs. ET-1 and acetylcholine were also infused with the specific ETA-receptor blocker FR-139317 (5 microg x kg[-1] x min[-1]; group II, n=6; group IV, n=6). Acetylcholine was also infused with the combined ET-receptor blocker, bosentan (0.5 mg/kg plus 1 mg x kg[-1] x h[-1], group V, n=5). The ETB-receptor agonist sarafotoxin 6c (5 ng x kg[-1] x min[-1]; n=4) was also infused. The percentage change in coronary artery diameter (%deltaCAD) to the infusions was measured at baseline and after 10 weeks of high-cholesterol diet in all animals. Sarafotoxin 6c mildly reduced %deltaCAD at baseline and 10 weeks (-10+/-2% and -12+/-3%, respectively). FR-139317 did not attenuate the epicardial vasoconstrictor response to ET-1 at baseline (%deltaCAD -18+/-8% for group I versus -12+/-6% for group II; P=NS) but did at 10 weeks (...Continue Reading

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Citations

Feb 25, 1999·Atherosclerosis·D HasdaiA Lerman
May 14, 1998·The Journal of Laboratory and Clinical Medicine·C R CannanA Lerman
May 2, 2002·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Alexei V Agapitov, William G Haynes
Jul 4, 2003·Canadian Journal of Physiology and Pharmacology·Michel Lavallée, Eric Thorin
Oct 17, 2003·Coronary Artery Disease·Matthias BartonChristian C Haudenschild
Apr 17, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Brielle L DotsonSteven K Malin

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