Effect of long-term streptozotocin-induced diabetes on coronary vasoconstriction in isolated perfused rat heart

Abstract

The primary goal of this study was to investigate the effect of long-term (9 months) streptozotocin (STZ)-induced diabetes on the coronary vasoconstrictor responses to vasoactive agents such as high K+, acetylcholine (ACh), endothelin-1 (ET-1), and the calcium-channel activator Bay K 8644. For this, we used isolated rat hearts perfused at constant flow rate. Each of the four agents caused dose-dependent increases in perfusion pressure in isolated hearts from age-matched control and STZ-induced diabetic rats. The dose-response curves for high K+, ACh, and ET-1 were shifted to the left, so that at some lower doses of these agents the increased perfusion pressure was greater in coronary arteries obtained from diabetic rats than in those from control rats. On the other hand, the maximum contractile response induced by each of these agents was lower in the diabetic perfused heart. The Bay K 8644-induced contractile response was significantly greater in the coronary arteries of diabetic rats than in those of control rats. A threshold-constrictor concentration of Bay K 8644 (1 nM) potentiated the ACh-induced vasoconstriction in coronary arteries from both groups, and the potentiated responses were greater in diabetic rats than in controls at lower concentrations of ACh (100 nM and 1 μM). These findings suggest that the coronary artery contractile responses to lower concentrations of ACh or ET-1 are exaggerated in long-term STZ-induced diabetic hearts. These changes may be due to alterations in the activity of voltage-gated Ca2+ channels.