Y. Kohno et al., HETEROGENEITY OF ALPHA(1)-ADRENOCEPTOR SUBTYPES INVOLVED IN ADRENERGIC CONTRACTIONS OF DOG-BLOOD VESSELS, British Journal of Pharmacology, 112(4), 1994, pp. 1167-1173
1 We determined the alpha(1),-adrenoceptor subtypes involved in adrene
rgic contractions of eight different blood vessels isolated from the d
og. 2 Noradrenaline produced concentration-dependent contractions in a
ll the blood vessels tested, which were competitively inhibited by pra
zosin, WB4101, HV723 and 5-methylurapidil. However, there was consider
able difference between the vessels with regard to the pK(B) values fo
r all the antagonists. The alpha(1)-adrenoceptors of dog vertebral and
carotid arteries had high affinity for prazosin (pK(B)>9.0) but low a
ffinity for WB4101 (<8.5), 5-methylurapidil (<7.5) and HV723 (<less th
an or equal to 8.5). By contrast, HV723 had higher affinity (>9.0) tha
n prazosin (<8.3), WB4101 (<8.7) and 5-methylurapidil (<8.2) in the po
rtal vein, mesenteric artery and vein, and renal artery. In the femora
l artery and vein, however, the four antagonists showed pK(B) values i
n the range 8.0-8.7. 3 Chloroethylclonidine (10 mu M) produced a remar
kable reduction of the contractile responses to noradrenaline in the v
ertebral and carotid arteries as compared with those. in the other ves
sels. Nifedipine inhibited the responses to noradrenaline in all the t
issues tested, and had marked effects in the portal vein. 4 Sympatheti
c adrenergic contractions induced by transmural electrical stimulation
were also inhibited by prazosin and HV723 at different potencies amon
g tissues. The relative potencies of both the antagonists paralleled t
he relationship in inhibiting the responses to exogenous noradrenaline
in each vessel. 5 According to recent alpha(1)-adrenoceptor subclassi
fication, the present results suggest that the contractions of blood v
essels induced by endogenous and exogenous noradrenaline are mediated
through different alpha(1)-adrenoceptor subtypes heterogeneously distr
ibuted in each vessel; presumably, the alpha(1B) subtype in the caroti
d and vertebral arteries, the alpha(1N) subtype in the visceral region
and the alpha(1L) subtype in the femoral region. Regionally different
expression of alpha(1)-adrenoceptor subtypes may be in part associate
d with he regional heterogeneity of sympathetic responses in the blood
vessels.