Removal of the endothelium potentiates canine large coronary artery constrictor responses to 5-hydroxytryptamine in vivo.

Abstract

SUMMARY. Recent studies in isolated epicardial coronary artery rings have shown that the endothelium modulates vasomotor responses to certain endogenous neurohumoral agents. It is not known whether the endothelium plays a role in large coronary vasoregulation in the intact coronary circulation. Accordingly, we examined effects of endothelial removal on vasoconstrictor responses of the proximal coronary artery in anesthetized adult mongrel dogs. The left anterior descending artery was perfused at 100 mm Hg with arterial blood from a pressurized reservoir. Coronary diameter was measured continuously with 7-MHz sonomicrometer crystals attached to the adventitia of the artery. Fifteen minutes after mechanical disruption of the endothelium with a balloon-tipped catheter, baseline diameter was unchanged from a control value of 2.60 ± 0.13 mm (mean ± SE, n = 17). Endothelial denudation resulted in a dose-dependent potentiation of the constrictor response to intracoronary 5-hydroxytryptamine (1-50 jig/min, n = 8). With the endothelium intact, a 5 /ig/min infusion of 5-hydroxytryptamine reduced diameter by 24 ± 14 /im, while a 50 /ig/min dose reduced diameter by 54 ± 25 fim. After endothelial removal, the decrease in diameter averaged 74 ± 18 ^m at 5 jjg/min and 132 ± 29 /im at 50 jig/min, indicating a 10-fold increase in the sensitivity to 5-hydroxytryptamine. The constrictor responses to angiotensin II (1 and 5 jig/min, n = 7) and phenylephrine (1-5 /ig/min, n = 7) were not altered by endothelial removal. Thus, endothelial removal selectively potentiates the constrictor responses to 5-hydroxytryptamine in the intact coronary circulation of the dog. (Cite Res 57: 46-54, 1985) RECENT studies in isolated arterial preparations including coronary arteries have demonstrated an obligatory role for endothelial cells in the response of vascular smooth muscle to various neurohumoral agents. Removal of the endothelium abolishes vasodilator responses to acetylcholine, bradykinin, thrombin, and substance P (Furchgott and Zawadzki, 1980;Furchgott, 1983) and potentiates vasoconstrictor responses to 5-hydroxytryptamine (Cohen et al., 1983a;Cocks and Angus, 1983).Recently, Cohen and co-workers (1983b) demonstrated that aggregating autologous platelets cause contraction of isolated coronary artery segments. The contractions were augmented after removal of the endothelium, and were attenuated by the 5-hydroxytryptamine antagonists, ketanserin and cyproheptadine. These investigators have also demonstrated that when coronary artery segments are precontracted with prostaglandin F 2a , 5-hydroxytryptamine results in relaxation in some rings with endothelium, but results in contraction in all rings with the endothelium removed. These data suggest that the response of isolated large coronary arteries to 5-hydroxytryptamine is the net result of a direct constrictor effect on the smooth muscle which is opposed by a dilator response mediated by the endothelium (Cohen et al., 1983a). These in vitro observations have suggested that the absence o...

Acute hypertension selectively potentiates constrictor responses of large coronary arteries to serotonin by altering endothelial function in vivo.

“…Second, the potentiation of the constrictor response to serotonin following hypertension was comparable to that observed during normotension following mechanical removal of endothelium. 9 Third, removal of endothelium prior to hypertension abolished the effects of hypertension on constrictor responses to serotonin. Since a dose-dependent vasoconstrictor response to serotonin was observed following removal of endothelium, the failure of hypertension to potentiate responses cannot be explained by maximum constriction following endothelial removal.…”

“…8 We have previously examined the role of endothelium on responses of large coronary arteries to vasoconstrictors in the intact circulation. 9 Mechanical removal of endothelium selectively augmented constriction of coronary arteries to serotonin. The present studies were undertaken to test the hypothesis that acute hypertension results in altered vasomotor responses in the coronary circulation that persist beyond the duration of hypertension.…”

Aggregating human platelets cause direct contraction and endothelium-dependent relaxation of isolated canine coronary arteries. Role of serotonin, thromboxane A2, and adenine nucleotides.

“…We therefore speculate that coronary vasospasm may be, in at least some instances, due to endothelial dysfunction. In one animal model, intact endothelium reduced vasoconstriction to serotonin in blood-perfused canine coronary arteries (27); in another, intact endothelium prevented the development of platelet-induced coronary spasm in fluorocarbon-perfused isolated rabbit hearts (28). Our results suggest that blockade ofthe synthesis by platelets ofthromboxane A2, or of the appropriate vascular serotonergic or thromboxane receptors, may be of therapeutic benefit in coronary vasospastic disease; both may be required for full effect.…”

Rapid baroreceptor resetting in chronic hypertension. Implications for normalization of arterial pressure.

“…1316 - 18 A low resistance stainless steel clip holding two miniature piezoelectric crystals (5 MHz) was placed across the carotid sinus and sutured to the adventitia. The diameter of the sinus was determined from the transit time of acoustic signals between the crystals.…”