Existence of Functional α1A- and α1D- but No α1B-Adrenoceptor Subtypes in Rat Common Carotid Arteries

Abstract

ABSTRACT-Using the cannula inserting method, vasoconstrictor responses to a1-adrenoceptor agonists (noradrenaline [NA], phenylephrine [PE] and methoxamine [ME]) and effects of a 1-adrenoceptor antagonists (WB4101, chloroethylclonidine [CEC] and BMY7378) were investigated in isolated and perfused rat common carotid arteries. The rank order of agonist potency and efficacy was NA = PE > ME. Either WB4101 or BYM7378 inhibited NA-and PE-induced constrictions in a dose-related manner. CEC did not inhibit the NA-and PE-induced responses. The ME-induced responses were also significantly blocked by either WB4101 or BMY7378. From these results, it is concluded that there are functional a 1A-and a1D-adrenoceptor subtypes in rat common carotid arteries, but no functional a1B subtype.Keywords: Cannula inserting method, Rat common carotid artery, a1-Adrenoceptor subtype Previously, in isolated rat common carotid arteries we investigated pharmacological features of vascular responses (1), using the cannula insertion technique (2, 3). It was demonstrated that noradrenaline and phenylephrine caused a long-lasting vasoconstriction (30 -60 min) even in a single injection of each compound, although other vasoconstrictor compounds (5-HT, PGF2=, angiotensin II or KCl) caused a relatively short-lasting constriction (within 20 min), indicating that this artery responded well to the a 1-adrenoceptor agonist. On the other hand, selective a2-adrenoceptor agonists, clonidine and xylazine, did not cause any vascular response in the same arterial preparation, indicating that there are no functional a2-adrenoceptors (1). Thus, it is interesting to clarify the a1-adrenoceptor subtypes in the rat common carotid artery. a1-Adrenoceptors are a heterogeneous family of G-protein coupled receptors. It is recognized that there are three functional a1-adrenoceptor subtypes, a1A, a1B and a1D, corresponding to the cloned subtypes, a 1a, a1b and a1d, respectively (4, 5). Recently, a selective a 1D-adrenoceptor antagonist, BMY7378, was introduced (6). Therefore, in the present study we investigated the postsynaptic a1-adrenoceptor subtypes of the isolated rat common carotid artery by using selective a1A-, a1B-and a1D-adrenoceptor subtype antagonists (WB4101, chloroethylclonidine and BMY7378, respectively). MATERIALS AND METHODSMale Wistar rats (weighing an average of 220 g, aged 7 weeks) were used in this study. After ether anesthesia and treatment with sodium heparin (200 units/ kg, i.v.), these animals were sacrificed by rapid exsanguination and then the common carotid artery was excised and immersed immediately in cold Ringer solution at 4°C. Isolated common carotid arteries that were 10 to 11 mm in length and 0.8 to 0.9 mm in outer diameter were selected for study. A stainless steel cannula with small holes 2 mm from the distal sealed end (25 gauge and 3 cm in length) was carefully inserted into each vessel segment to avoid injury of the intraluminal surface of the isolated vessel. Segments were set up in the bath for preparation as described by Tsu...

Cross-talk with β2-adrenoceptors enhances ligand affinity properties from endothelial alpha1D-adrenoceptors that mediates carotid relaxation

“…α 1D ‐ARs mediate both relaxation and contraction induced by PhE in rat carotid . We confirmed these findings, pointing an important dual opposite effect mediated by α 1D ‐ARs on carotid tone.…”

“…This analysis is reliable because antagonist potency represents an accurate estimative of receptor affinity . BMY7378 is a well‐known reversible competitive antagonist of α 1D ‐ARs, and the appropriated equilibrium time for the antagonist (30 min) was reached during our bioassays. Interestingly, we showed that BMY7378 produced an unsurmountable antagonism on PhE‐induced relaxation despite its classical surmountable antagonism on PhE‐induced contraction.…”

Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats

“…Their antagonists can relax the arteriole and vein so as to decrease the standing and lying blood pressure. There are functional α 1A -and α 1D -adrenoceptor subtypes in response to the vasoconstriction of the rat common carotid arteries, but no α 1B -adrenoceptor subtype [10] . The analysis of mutant mice has provided some insight into the physiological role of each α 1 -adrenoceptor subtype in the regu- lation of blood pressure.…”

Pharmacological characterization ofα1‐adrenoceptors in equine digital veins

“…, 1997; Yan et al. , 2001; Chiba & Tsukada, 2002). The aim of the present study was to characterize the postsynaptic α 1 ‐adrenoceptor subtype(s) mediating vasoconstrictor function in isolated EDVs by the use of selective agonists and antagonists.…”

“…The α 1 ‐adrenoceptor subtypes are important mediators of smooth muscle contraction and hypertrophic growth (Piascik & Perez, 2001) and their presence in the vasculature has been reported in a variety of species, including the rat (Chiba & Tsukada, 2002; Arévalo‐León et al. , 2003), rabbit (Satoh et al.…”