α₂‐Adrenoceptor agonists enhance responses to certain other vasoconstrictor agonists in the rat tail artery

Abstract

1 The effects of the a2-adrenoceptor agonists clonidine, rilmenidine, TL99 and UK14304 on the vasoconstrictor response to sympathetic nerve stimulation and on the concentration-response curves to noradrenaline and phenylephrine were compared in two isolated, perfused vascular tissues: the rat tail artery (which has both postjunctional al-and a2-adrenoceptors), and the rabbit ear artery (in which only cx-adrenoceptors are present postjunctionally). 2 In the rabbit ear artery, the first observable effect of a2-adrenoceptor agonists was inhibition of vasoconstrictor responses to sympathetic nerve stimulation. This occurred with concentrations of the M2-adrenoceptor agonists which were far below those producing vasoconstriction. Responses to noradrenaline were not affected. 3 In contrast, in the rat isolated perfused tail artery, a2-adrenoceptor agonists, in concentrations that produced no other observable effects, enhanced the vasoconstrictor responses to sympathetic nerve stimulation and to noradrenaline. Much higher concentrations of a2-adrenoceptor agonists produced vasoconstriction in most preparations and only then reduced the response to sympathetic nerve stimulation. The enhancing effect of CX2-adrenoceptor agonists was blocked by idazoxan, but not by prazosin.4 Vasoconstrictor responses in the rat tail artery to the relatively selective xl-adrenoceptor agonist phenylephrine were enhanced by X2-adrenoceptor agonists. The enhancement of the response to phenylephrine was greater than that to the mixed a1-and a2-adrenoceptor agonist noradrenaline. 5 Vasoconstrictor responses in the rat tail artery to vasopressin, ATP and KCl, like those to a1-adrenoceptor agonists, were enhanced by a2-adrenoceptor agonists. However, vasoconstrictor responses to 5-hydroxytryptamine and angiotensin II were not enhanced.

Influences of the endothelium and hypoxia on α1‐ and α2‐adrenoceptor‐mediated responses in the rabbit isolated pulmonary artery

“…It has previously been suggested that, in certain vascular beds, simultaneous activation of l-and M2-adrenoceptors is required before the responses to a2-adrenoceptor stimulation are observed, e.g. in the rabbit saphenous artery (Dunn et al, 1991b) and rat tail artery (Xiao & Rand, 1989). It is likely, therefore, that such interactions may involve complex facilitatory interactions between alr-and M2-adrenoceptor-induced calcium ion channel activation and membrane potential changes.…”

5-Hydroxytryptamine–Induced Potentiation of Endothelin-1– and Norepinephrine-Induced Contraction Is Mitogen-Activated Protein Kinase Pathway Dependent

“…The 5-HT receptor is of the 5-HT 2 receptor class 21 (supported by inhibition of 5-HT-induced contraction by the 5-HT 2 receptor antagonist LY53857), the ET-1 receptor is an ET A receptor, 22 and the ␣-adrenergic receptor is a mixture of ␣ 1 -and ␣ 2 -adrenergic receptors. 23,24 All 3 classes of receptors activate similar, classic signaling pathways (plasma membrane calcium channels and phospholipase C), and all receptors have recently been identified as being able to activate the Erk MAPK pathway in vascular smooth muscle. Several investigators have demonstrated that Erk MAPK can phosphorylate caldesmon and, in doing so, release the calmodulin-mediated inhibition of actinomyosin ATPase and thereby promote smooth muscle contraction.…”

Pharmacological profile of the novel .ALPHA.-adrenoceptor antagonist KT-611(naftopidil).

“…Activation of the postjunctional a2-adrenoceptors not only causes a direct contractile action but also en hances the responses to various contractile agents (5,18,19). Therefore, it is likely that, like KT-611, the drugs which have an antago nistic action to both postjunctional a 1 and a2 adrenoceptors may become more beneficial for the control of adrenergic responses in blood vessels and other tissues.…”