Alpha-1 and alpha-2 adrenoceptor agonists induce vasoconstriction of the normotensive rat caudal artery in vitro by stimulation of a heterogeneous population of alpha-1 adrenoceptors

Abstract

Although alpha-2 adrenoceptor agonists rapidly induce arterial vasoconstriction in vivo, such responses have proven difficult to obtain in vitro. We have investigated the vasoconstrictor effects of various alpha-1 and alpha-2 adrenoceptor agonists in the perfused superfused caudal artery of the normotensive rat. Intrinsic activities were; methoxamine; 1, phenylephrine; 0.94, noradrenaline; 0.93, guanfacine; 0.88, clonidine; 0.47, UK 14,304 [5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline tartrate]: 0.10, azepexole; 0. Antagonism by the selective alpha-1 agent, prazosin of the vasoconstrictor responses provoked by methoxamine, guanfacine or clonidine, showed a high affinity with--log KB values in the range of 8.5 to 9.4. There were no significant differences between the KB values obtained with the three agonists. Antagonism by the selective alpha-2 antagonist, yohimbine showed a low affinity with KB values between 6.7 to 7.6 for the three agonists. The calcium entry blocker, nicardipine, antagonized responses to clonidine at nanomolar concentrations and those to phenylephrine at micromolar concentrations. We conclude that vasoconstrictor responses in this isolated tail artery preparation are primarily mediated via an alpha adrenoceptor which can be classified, on the basis of the results with specific antagonists, as being of the alpha-1 type. The results obtained with nicardipine suggest that the population of alpha adrenoceptors is not, however, homogeneous.

Transient supersensitivity to α‐adrenoceptor agonists, and distinct hyper‐reactivity to vasopressin and angiotensin II after denervation of rat tail artery

“…The tissues were exposed to each concentration for 5 min, followed by a washout period during which the tension returned to the baseline value before addition of the next concentration of agonist. In tail artery, the pA 2 for the α 1 ‐adrenoceptor‐selective antagonist prazosin in antagonizing the effects of phenylephrine and methoxamine is in the range 9–9.5 (Abel and Minneman, 1986; Atkinson et al. , 1988) and, in preliminary experiments, we ascertained that the pA 2 for the α 2 ‐adrenoceptor‐selective antagonist rauwolscine in antagonising the effects of clonidine is ∼9.…”

Pharmacological characterization of an α1A‐adrenoceptor mediating contractile responses to noradrenaline in isolated caudal artery of rat

“…It has been shown previously that the caudal artery of rat contains functional a 2 -adrenoceptors (Medgett & Langer, 1984;Atkinson et al, 1988). Although these post-junctional a 2adrenoceptors may play a prominent vasoconstrictor role in vivo (Redfern et al, 1995), when assayed in vitro, they contract tissue only when basal tension is elevated by prior application of another spasmogen (Templeton et al, 1989;MacLean & McGrath, 1990).…”

Effect of NG‐nitro‐L‐arginine methylester (L‐NAME) on functional and biochemical α1‐adrenoceptor‐mediated responses in rat blood vessels

“…Smooth muscle contraction induced by a-adrenoceptor agonists in rat aorta is mostly if not exclusively mediated by aladrenoceptors (Ruffolo, 1985). Nevertheless, some (Weiss et al, 1983;Vila et al, 1993) but not all (Atkinson et al, 1988) studies have suggested that a, and a2-adrenoceptors are present in rat tail artery. Thus, in our experimental protocol, yohimbine (0.1 jIM) was present to prevent the stimulation of a2-adrenoceptors by agonists.…”