Modulation by Aging of the Coronary Vascular Response to Endothelin-1 in the Isolated Perfused Rat Heart

Abstract

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide generated by vascular endothelial cells. It has been reported that ET-1 induces transient vasodilation prior to a long-lasting vasoconstrictor response in the coronary vessels of the rat. Since the dilator response to ET-1 requires intact endothelium, substances such as endothelium-delived relaxing factor (EDRF) and prostacyclin released from endothelial cells may play a role in the vasodilation. These substances may counteract the vasoconstriction induced by ET-1 in the coronary vessels. Therefore changes in endothelial function may be responsible for age-related alterations in vascular responsiveness, thereby contributing to the increased incidence of cardiovascular disorders seen in aged populations. We studied the influence of aging on the coronary vascular response to ET-1, with special attention to the involvement of EDRF, in the isolated perfused rat heart. We used 2-, 6- and 24-month-old (mo) male Fisher 344 rats in this study. Hearts were perfused at a constant pressure by the Langendorff technique, using modified Krebs-Henseleit solution (36°). ET-1 injected as a single bolus (0.3, 3, and 30 nmol) reduced the coronary flow in all groups. In half of the 2-mo group injected with 0.3 nmol of ET-1, an initial transient vasodilation prior to vasoconstriction was observed; this was abolished by hemoglobin (100 μmol/min). ET-1 (30 nmol) induced a more pronounced vasoconstriction in 6- and 24-mo than in 2-mo rats.