Intracoronary endothelin-1 increases coronary retrograde pressure by constricting arterioles.

STUDY OBJECTIVE

The aim was to determine the site of coronary vasoconstriction induced by endothelin, by investigating the response in terms of retrograde pressure and reactive hyperaemia.

EXPERIMENTAL MATERIAL

Twelve anaesthetised mongrel dogs, 12-14 kg, were used for the studies.

DESIGN

The left anterior descending coronary artery was cannulated and perfused with blood through an extracorporeal bypass. The effects of intracoronary endothelin-1 (1-500 pmol) on coronary blood flow, coronary flow reserve (the peak reactive flow and the repayment after 15 s coronary occlusion), and retrograde coronary pressure during coronary occlusion were studied (n = 7). The retrograde coronary flow was collected from the bypass at each dose (n = 5).

MEASUREMENTS AND MAIN RESULTS

At doses of greater than 20 pmol the coronary flow decreased dose dependently and reached almost zero flow at 500 pmol. The coronary flow reserve also decreased; however, the retrograde pressure was raised dose dependently at doses of greater than 10 pmol. At a dose of 500 pmol, the retrograde pressure was increased to 61 mm Hg [82(SEM 12)% of the coronary perfusion pressure]. Retrograde flow remained unchanged throughout the experiment.

CONCLUSIONS

The endothelin-1 induced rise in retrograde pressure is in accordance with a dose dependent reduction in coronary flow reserve, and collateral flow was not augmented by endothelin. It is concluded that the effect of endothelin-1 on coronary circulation in situ was mainly due to the constriction of small resistant vessels.