Effect of acute hypertension in the coronary circulation: role of mechanical factors and oxygen radicals.
OBJECTIVE
In previous studies severe, acute hypertension damaged the endothelium in proximal coronary arteries and selectively potentiated constriction of the artery to serotonin. In the present study we investigated the role of several mechanical factors and of oxygen radicals in this response.


METHODS
To test the role of mechanical factors in the response to acute hypertension, the effect of different magnitudes of elevation of perfusion pressure and the rate of the rise in perfusion pressure were studied. Pharmacologically induced increases in blood pressure were produced by infusion of angiotensin II or phenylephrine. The role of oxygen radicals was tested by measuring responses to serotonin before and after increases in perfusion pressure in dogs treated with a combination of superoxide dismutase and catalase or with deferoxamine.


METHODS
In open-chest anesthetized dogs the diameter of the left anterior descending coronary artery (LADCA) was measured using sonomicrometer crystals, and the LADCA was perfused at a constant pressure of 80 mmHg from a reservoir. Responses to serotonin were measured at this perfusion pressure before and after an abrupt increase in perfusion pressure.


RESULTS
Intracoronary serotonin (5 or 50 micrograms/min) produced a dose-dependent constriction of the LADCA while increasing coronary flow. Abruptly increasing the coronary perfusion pressure from 80 to 120, 150 or 200 mmHg augmented the constriction to serotonin twofold, whereas increases in perfusion pressure to 100 mmHg had no effect. Increasing coronary pressure slowly (over a 4-min period) from 80 to 200 mmHg augmented constriction to serotonin. Inducing acute hypertension (coronary pressure 200 mmHg) pharmacologically with angiotensin II also augmented constriction to serotonin, whereas phenylephrine-induced hypertension did not. Superoxide dismutase, a scavenger of superoxide anions and catalase, a scavenger of hydrogen peroxide, prevented the augmented constriction to serotonin following a pressure increase. Deferoxamine, which prevents generation of hydroxyl radicals from superoxide anions and hydrogen peroxide, also prevented the enhanced constriction to serotonin following an acute pressure increase.


CONCLUSIONS
Moderate physiological increases in pressure, induced either mechanically or pharmacologically, can augment the responses to serotonin. Oxygen-derived free radicals, particularly hydroxyl radicals, might be involved in the abnormal response to serotonin following an abrupt increase in coronary pressure.
V H
VH
De Bruyn
D W
DW
Nuno
M
M
Cappelli-Bigazzi
W P
WP
Dole
K G
KG
Lamping
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003676:Deferoxamine / Q000494:pharmacology; D004285:Dogs; D004357:Drug Synergism; D005260:Female; D005609:Free Radicals; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D005609:Free Radicals; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D010656:Phenylephrine; D012701:Serotonin; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine