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.

Localization of endothelin receptors in bleomycin-induced pulmonary fibrosis in the rat

“…We did not detect ET A receptor immunoreactivity on lung fibroblasts. In our previously published study, we observed a clear signal for ET A receptor mRNA in cardiac fibroblasts by in situ hybridization but no ET A receptor immunoreactivity (Wendel-Wellner et al 2002). This might relate to cell type-specific posttranslational modifications at the C-terminus of the ET A receptor protein (Horstmeyer et al 1996), where the epitope recognized by the antiserum is located contributing to the observed physical heterogeneity of the ET A receptor (Shraga-Levine and Sokolovsky 1998).…”

“…RT-PCR for ET A and ET B receptor mRNA was performed essentially as described before (Wendel-Wellner et al 2002). Rat porphobilinogen deaminase (PBGD) served as housekeeping gene (Fink et al 1999).…”

Muscular ETBReceptors Develop Postnatally and Are Differentially Distributed in Specific Segments of the Rat Vasculature

“…While Hori et al (1992) did not detect ET B receptor mRNA in coronary vessels by in situ hybridization, our findings are in line with the reports by Goodwin et al (1999) and Balwierczak (1993), who demonstrated coronary vasoconstriction by ET A and ET B receptor stimulation. In a previous study, we reported that both ET A and ET B receptors colocalize on coronary arterial smooth muscle cells (Wendel-Wellner et al 2002). The ET B receptor antiserum used in this study was directed against an epitope at the carboxy terminus of the ET B receptor molecule and also recognized ET B receptors on endothelial cells.…”

“…While the role of the ET A receptor subtype in mediating vasoconstriction is beyond debate, the existence of ET B receptors on vascular smooth muscle cells in distinct vascular beds is still controversial, and systematic histological investigations on the distribution pattern of vascular ET receptors are missing. Recently, colocalization of ET A and ET B receptors on arterial smooth muscle cells in the coronary circulation (Wendel-Wellner et al 2002) and small pulmonary arteries of adult rats were demonstrated (Soma et al 1999).…”

Distribution of Endothelin Receptor Subtypes ETA and ETB in the Rat Kidney

“…ET B receptor stimulation has been coupled to the release of nitric oxide (NO) and prostacyclin (Hyslop and de Nucci 1992), leading to vasodilation. In addition, presence of ET B receptors on vascular smooth muscle cells has been observed in different vascular beds (Wendel-Wellner et al 2002;Wendel et al 2005), and the ET B receptor subtype was considered to be the main receptor mediating ET-1-induced renal vasoconstriction in the rat (Wellings et al 1994;Endlich et al 1996). …”