Cellular localization of the endothelin receptor subtypes ET_A and ET_B in the rat heart and their differential expression in coronary arteries, veins, and capillaries

Abstract.

In the heart, the endothelin (ET)/endothelin-receptor system is markedly involved in pathophysiological mechanisms underlying various cardiac diseases. Based upon pharmacological studies both ET-receptor subtypes take part in the regulation of coronary vascular tone, however, their detailed cellular distribution in the coronary vascular bed based upon direct mRNA and protein detection is unknown. This issue was addressed in the rat heart by means of non-radioactive in situ hybridization, RT-PCR, and immunohistochemistry. Expression of vascular ET_A-receptors was detected in arterial smooth muscle and capillary endothelium while ET_B-receptors were present in arterial, venous, and capillary endothelium, and in arterial and venous smooth muscle cells. This differential distribution of the ET-receptor subtypes supports the concept that ET_A- as well as ET_B-receptors mediate arterial vasoconstriction, while postcapillary vascular resistance is exclusively regulated by ET_B-receptors. The observed capillary endothelial expression of the ET_A-receptor correlates with the known ability of ET_A-receptor antagonists to attenuate increases in cardiac microvascular permeability during endotoxin shock and ischemia/reperfusion injury.