Effect of endothelin on sex-dependent regulation of tone in coronary resistance vessels.

BACKGROUND/AIMS: Sex dependent differences in coronary artery vasoregulation may be due to variations in responses to endogenous vasoactive compounds including endothelin (ET-1) and nitric oxide (NO).

METHODS: Septal coronary arteries (<200 μm) from healthy, sexually mature male, female and ovariectomized (i.e. surgical menopause) Sprague-Dawley rats were used. Myogenic tone, measured by pressure myography, was initially determined for all vessel segments studied before and after exposure to the nonselective ETA /ETB receptor blocker, bosentan (1 μM). Vasoconstrictor responses (vascular endothelium intact) to cumulative ET-1 (10-12 - 10-9  M) were assessed in a separate set of septal coronary vessels. Additional studies, examined the vasoconstrictor effects of ET-1 after NO blockade with L-NAME (200 μM).

RESULTS: Myogenic tone was 26 ± 7% in male, 20 ± 7% in female (p = 0.04 versus male) and 24 ± 3% in ovariectomized (p = NS versus male/female) vessels. Antagonism of ET-1 receptors produced a greater reduction in myogenic tone in male, compared to female rats over a similar range of intraluminal pressure (20-80 mmHg). Robust constrictor responses to cumulative concentrations of ET-1 were observed in all vessels; however, male rats exhibited greater sensitivity to vasoconstrictor effects of ET-1. After exposure to L-NAME vessel responses to ET-1 were normalized in male and female (not studied in ovariectomized) groups.

CONCLUSIONS: These findings confirm marked sex differences for myogenic tone and vessel constrictor responses to ET-1 in coronary resistance vessels. Results also suggest greater sensitivity to vasoconstrictor effects of ET-1 in male coronary resistance vessels.