Postsynaptic alpha 2-adrenergic receptor-mediated vasoconstriction in SHR tail arteries in vitro.

Abstract

In isolated perfused tail arteries of spontaneously hypertensive rats (SHR), the selective alpha 2-adrenergic receptor antagonist idazoxan ( RX781094 ) at low concentrations antagonized vasoconstrictor responses induced by norepinephrine (NE) and low frequency periarterial field stimulation. The vasoconstrictor responses to the selective alpha 2-adrenergic receptor agonist TL99 or to phenylephrine were also antagonized by low concentrations of idazoxan . In contrast, idazoxan did not antagonize responses induced by the alpha 1-adrenergic receptor agonists amidephrine or methoxamine in perfused tail arteries of SHR. The alpha 1-adrenergic receptor antagonist prazosin was very potent against methoxamine or phenylephrine and responses to periarterial field stimulation in SHR and Wistar-Kyoto (WKY) rat tail arteries, but only showed a modest selectivity for TL99 -induced responses in SHR arteries. The results support the contention that postjunctional alpha 2-adrenergic receptors can be demonstrated in arterial smooth muscle in vitro and are particularly evident in arteries from hypertensive animals. In SHR tail arteries, postsynaptic alpha 2-adrenergic receptors contribute to the vasoconstrictor responses to exogenous NE and may be activated by endogenously released NE.

Effects of reduced calcium ion concentration and of diltiazem on vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation in rat isolated tail artery

“…In conclusion, the effects of idazoxan and prazosin on responses to NA and SNS confirm previous data Hicks et al, 1984), suggesting that ai-adrenoceptors predominate in proximal segments of rat tail artery, but that there exists a subpopulation of smooth muscle a2-adrenoceptors; in the present instance, neuronal uptake and fadrenoceptors were not blocked. Exogenous agonists activate both oz1-and aC2-subtypes whereas NA released from nerve terminals almost exclusively activates a1-adrenoceptors; this may be attributed to a hypothetical differential intramural distribution of ol-and 02-adrenoceptors in arterial smooth muscle (see Introduction).…”

“…Smooth muscle CX2-adrenoceptors have been identified previously in proximal segments of tail arteries of SHR and Sprague-Dawley rats, by use of the agonists NA, methoxamine and TL99 in combination with the antagonists idazoxan, prazosin and corynanthine (see Hicks et al, 1984;. The most direct evidence for the presence of smooth muscle X2-adrenoceptors was the effect of the selective a2-adrenoceptor agonist TL99 (Hicks & Cannon, 1981): in SHR tail arteries, responses to TI99 were substantially reduced by idazoxan (100 nmol 1-'), unaffected by prazosin (1 nmol 11) and virtually abolished if the extracellular calcium concentration was halved .…”

“…Only very recently has the existence of smooth muscle cX2-adrenoceptors been demonstrated in a peripheral, well-innervated muscular artery in vitro, using the rat isolated tail artery preparation Hicks et al, 1984). The presence of both a1-and a2-subtypes on smooth muscle cells in rat tail arteries was reported in the latter studies, based on the effects of idazoxan (selective a2-adrenoceptor antagonist; Doxey et al, 1983) and prazosin (selective cx1-adrenoceptor antagonist) on responses to NA and to TL99 (selective a2-adrenoceptor agonist; Hicks & Cannon, 1981).…”

“…In previous studies Hicks et al, 1984) data were obtained under conditions of blockade of f-adrenoceptors and of inhibition of neuronal uptake using propranolol and cocaine, respectively. In the present study it was considered important to confirm that effects of selective a-adrenoceptor antagonists, as observed in the above studies, were qualitatively similar in the absence of blockade of ,B-adrenoceptors and neuronal uptake, since data from in vivo studies were obtained in the absence of these agents.…”

Dilation of forearm blood vessels after angiotensin-converting-enzyme inhibition by captopril in hypertensive patients.

“…33 A recent report suggests that postsynaptic a 2 receptors contribute significantly to the responses of rat tail arteries to norepinephrine in SHR but not in normotensive WKY rats. 56 The present study does not define the relative importance of the two a-adrenergic subtypes.…”