The effects of disease severity and sex on coronary endothelium-dependent vasomotor function in an atherosclerotic primate model.

BACKGROUND

The relationship between the extent of atherosclerosis and vascular reactivity is not known, since studies of humans have used indirect measures of the extent of atherosclerosis (angiography and ultrasound), and most patients studied had only minimal-to-moderate atherosclerosis. It is known that atherosclerosis impairs coronary vasodilatation in response to acetylcholine, and that estrogen improves vascular reactivity of atherosclerotic coronary arteries in women and perhaps in men. However, the effects of estrogen and sex on arteries with advanced, complicated plaques are not known.

METHODS

We used quantitative coronary angiography to measure vascular reactivity to infusions of 10(-6) mol/l acetylcholine and 15 micrograms/min nitroglycerin in 70 segments of coronary arteries in 16 rhesus monkeys (12 males, five intact females, nine ovariectomized females) with a wide range of extents of atherosclerosis. The extent and severity of atherosclerotic plaque in each segment was quantified by histologic and histomorphometric methods. Effects of sex and ovariectomy on vascular reactivity were examined at low and high levels of plaque severity.

RESULTS

Vascular responses ranged from constriction (by 18%) to dilatation (by 14%) compared with the control diameter. The magnitude of the vascular response to acetylcholine, either dilatation or constriction, decreased with increasing plaque severity (P < 0.01). At low severity, arteries of intact females dilated (by 7.2 +/- 2.1%), whereas those of males and ovariectomized females constricted (by 4.5 +/- 1.5% and 5.0 +/- 1.2%, respectively; P < 0.001, versus intact females). When lesions were severe, vascular responses did not differ among groups.

CONCLUSIONS

Our results indicate that arteries became unresponsive to acetylcholine as atherosclerotic lesions progressed in size and complexity, and that sex and estrogen status affected vascular reactivity only when lesions were small. These findings may imply a limited range of lesion development within which vascular reactivity can be influenced by sex and estrogen status.