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

Abstract

S U M M A R YThe endothelin/endothelin-receptor system is a key player in the regulation of vascular tone in mammals. We raised and characterized an antiserum against rat ET B receptor and investigated the distribution of ET B receptors in different vascular beds during postnatal development (day 0 through day 28) and in the adult rat. We report the tissuespecific and age-dependent presence of vasoconstrictor ET B receptors. At the time of birth, vascular smooth muscle cells from all tissues examined did not exhibit ET B receptor immunoreactivity. The occurrence of ET B receptor immunoreactivity in the postnatal development was time dependent and started in small coronary and meningeal arteries at day 5, followed by small mesenteric arteries as well as brachial artery and vein at day 14. At day 21, ET B receptors were present in the media of muscular segments of pulmonary artery, large coronary arteries, and intracerebral arterioles. At day 28, ET B receptor immunoreactivity was evident in interlobular renal arteries, vas afferens, and efferens. Large renal arteries, mesenteric artery, and elastic segments of pulmonary arteries, as well as coronary and mesenteric veins, did not exhibit ET B receptor immunoreactivity. These data demonstrate the age-dependent and tissue-specific presence of ET B receptors, mainly on arterial smooth muscle cells in the vascular system of the rat. E ndothelin -1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide (Yanagisawa et al. 1989). It takes part in the regulation of vascular tone after birth (for review see Perreault and Coceani 2003) and is implicated in the pathophysiology of cardiovascular, renal, and pulmonary diseases (Saito et al. 1990;Watanabe et al. 1990;Larriviere and Lebel 2003;Michel et al. 2003).ET-1 exerts its biological effects through two distinct ET-receptor subtypes, ET A and ET B . ET A receptors on smooth muscle cells exclusively mediate vasoconstriction, whereas ET B receptors can mediate both vasodilation as well as vasoconstriction, depending on their location on endothelial cells and vascular smooth muscle, respectively. 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).Pharmacological studies aimed at defining the role of vasoconstrictor ET B receptors are highly controversial, and studies from different groups lead to contradictory results even for identical organ systems (Takase et al.

Endothelin-A and -B receptors, superoxide, and Ca2+signaling in afferent arterioles

“…Such was also the case in membrane studies of both rat and rabbit renal microvessels, which showed that ET A R and ET B R are present in a proportion of 40:60 (5). Studies of the expression of ET B R in the neonatal rat kidney demonstrate that, by day 28 after birth, the interlobar artery develops immunofluorescent staining for ET B R (37). Interestingly, in this study, the main renal artery (as well as mesenteric and pulmonary arteries) was devoid of staining for ET B R, which suggests that conduit vessels express only ET A R (37).…”

Rapid functional upregulation of vasocontractile endothelin ETB receptors in rat coronary arteries

“…However, since the S6c-mediated vasoconstriction after 7 h incubation was not completely abolished in presence of U0126, this initial functional upregulation might involve additional mechanisms. Studies have shown that even fresh coronary arteries from healthy rats contain ET B receptor protein in VSMC (Wendel-Wellner et al 2002;Wendel et al 2005). Hence, we speculate that a part of the contractile ET B receptor upregulation may involve post-translational modifications of already expressed ET B receptors.…”

Age- and Sex-Specific Nociceptive Response to Endothelin-1

“…13,17,20,31,47,58 Exogenous administration of ET-1 evokes severe pain that is associated with allodynia in the injected limb in humans and spontaneous painassociated behaviors and allodynia/hyperalgesia in rodents. 12,14,34 With the increased recognition of developmental differences in pain and analgesia 21 and evidence that ET receptor expression changes with maturation and sex in a number of tissues, 1,27,41,56 we hypothesize that ET-1-induced nociception may be age-and sex-dependent. Male and female rats of 3 ages have been included: Postnatal day 7, 21, and 60 rats that model human infant, child, and young adult, respectively.…”