Heterogeneity of α₁‐adrenoceptor subtypes involved in adrenergic contractions of dog blood vessels

Abstract

1 We determined the al-adrenoceptor subtypes involved in adrenergic contractions of eight different blood vessels isolated from the dog. 2 Noradrenaline produced concentration-dependent contractions in all the blood vessels tested, which were competitively inhibited by prazosin, WB4101, HV723 and 5-methylurapidil. However, there was considerable difference between the vessels with regard to the pKB values for all the antagonists. The xl-adrenoceptors of dog vertebral and carotid arteries had high affinity for prazosin (pKB> 9.0) but low affinity for WB4101 (< 8.5), 5-methylurapidil (< 7.5) and HV723 ( < 8.5). By contrast, HV723 had higher affinity (>9.0) than prazosin (<8.3), WB4101 (<8.7) and 5-methylurapidil (<8.2) in the portal vein, mesenteric artery and vein, and renal artery. In the femoral artery and vein, however, the four antagonists showed pKB values in the range 8.0-8.7.3 Chloroethylclonidine (10 pM) produced a remarkable reduction of the contractile responses to noradrenaline in the vertebral and carotid arteries as compared with those in the other vessels. Nifedipine inhibited the responses to noradrenaline in all the tissues tested, and had marked effects in the portal vein. 4 Sympathetic adrenergic contractions induced by transmural electrical stimulation were also inhibited by prazosin and HV723 at different potencies among tissues. The relative potencies of both the antagonists paralleled the relationship in inhibiting the responses to exogenous noradrenaline in each vessel.5 According to recent xl-adrenoceptor subclassification, the present results suggest that the contractions of blood vessels induced by endogenous and exogenous noradrenaline are mediated through different xl-adrenoceptor subtypes heterogeneously distributed in each vessel; presumably, the aXB subtype in the carotid and vertebral arteries, the aIN subtype in the visceral region and the aIL subtype in the femoral region. Regionally different expression of a1-adrenoceptor subtypes may be in part associated with the regional heterogeneity of sympathetic responses in the blood vessels.

Heterogeneity of neurogenic responses in intra‐ and extrameningeal arteries of dogs

“…Simple contractions similar to those observed in the peripheral blood vessels of dogs (Muramatsu, 1991;Kohno et al, 1994) stimulation are sympathetic and adrenergic, and are mediated through ax-adrenoceptors. Recently, we demonstrated that the ax-adrenoceptors of dog vertebral and carotid arteries are of the a1B subtype (Kohno et al, 1994).…”

“…Rather, expression of receptors such as a-adrenoceptors and P2,Cpurinoceptors in the vascular smooth muscle cells appears to be controlled in regionally different ways, causing regional heterogeneity of sympathetic responses. Recently, we suggested that different subtypes of ax-adrenoceptors may be expressed in different tissues (Kohno et al, 1994;Muramatsu et al, 1995).…”

Prostatic α1-adrenoceptors and uroselectivity

“…A wide range of blood vessels contains the mRNA for all three subtypes [54]. Although species and vesseldependent, ␣ 1A , ␣ 1B , and ␣ 1D -adrenoceptors all seem to subserve the contractile response in vascular tissue [55][56][57][58]. On this basis, one could assume cardiovascular homeostasis depends on all the multiple subtypes, albeit to varying extents.…”

Functional evidence equating the pharmacologically‐defined α1A‐ and cloned α1C‐adrenoceptor: studies in the isolated perfused kidney of rat

“…This proposal received little attention due to possible alternative explanations, such as species variation , experimental rigour (Docherty et al, 1987;McGrath et al, 1989), and the potential for the involvement of M2-adrenoceptor subtypes (Bylund, 1985). It should be noted, however, that since the article by Flavahan & Vanhoutte (1986), aladrenoceptors exhibiting both high and low affinity for prazosin have been identified in gerbil (Kimura et al, 1993), rat (Oshita et al, 1991;Ohmura et al, 1992), rabbit (Muramatsu et al, 1990a;Oshita et al, 1993) and dog Kohno et al, 1994). Thus, a classification scheme proposing xl-adrenoceptor subtypes based upon divergent affinity estimates for prazosin remains in line with a body of current thinking (Muramatsu et al, 1990b;Oshita et al, 1991).…”