Alpha‐1D adrenoceptors are involved in reserpine‐induced supersensitivity of rat tail artery

Abstract

1 We examined reserpine-induced chemical denervation supersensitivity with special reference to alpha-1 adrenoceptor (AR) subtypes. 2 Chronic treatment with reserpine for 2 weeks depleted noradrenaline in the tail artery and spleen of rats. Noradrenaline in the thoracic aorta was negligible before and after reserpine treatment. 3 The treatment with reserpine produced supersensitivity in the contractile responses of the rat tail artery to phenylephrine, 5-HT and KCl, resulting in leftward shift of concentration-response curves (11.6-, 2.5-and 1.1-fold at EC 50 value, respectively). These results suggest a predominant sensitization of the alpha-1 AR-mediated response by reserpine treatment. 4 BMY 7378 at a concentration (30 nM) specific for blocking the alpha-1D AR subtype, but not KMD-3213 at a concentration (10 nM) selective for blocking the alpha-1A AR subtype, inhibited the supersensitivity of the phenylephrine-induced response in the reserpine-treated artery. On the other hand, the response to phenylephrine in reserpine-untreated artery was selectively inhibited by the same concentration of KMD-3213, but not by BMY 7378. Prazosin, a subtype-nonselective antagonist, blocked the responses to phenylephrine with the same potency, regardless of reserpine treatment. 5 In the thoracic aorta and spleen, no supersensitivity was produced in the responses to phenylephrine by reserpine treatment. 6 In a tissue segment-binding study using [ 3 H]-prazosin, the total density and affinity of alpha-1 ARs in the rat tail artery were not changed by treatment with reserpine. However, alpha-1D AR with high affinity for BMY 7378 was significantly detected in reserpine-treated tail artery, in contrast to untreated artery. Decreases in alpha-1A AR with high affinity for KMD-3213 and alpha-1B AR with low affinities for KMD-3213 and BMY 7378 were also estimated in reserpine-treated tail artery. 7 Alpha-1D AR mRNA in rat tail artery increased to three-folds by reserpine treatment, whereas the levels of alpha-1A and 1B mRNAs were not significantly changed. 8 The present results suggest that chronic treatment with reserpine affects the expression of alpha-1 AR subtypes of rat tail artery and that the induction of alpha-1D ARs with high affinity for catecholamines is in part associated with reserpine-induced supersensitivity.

Pressor responses to ephedrine are not impaired in dopamine β‐hydroxylase knockout mice

“…Chronic inhibition of the adrenergic system results in increased responses to exogenous adrenergic agonists (Taki et al, 2004). In the present study increased responses to noradrenaline and phenylephrine were not observed in Dbh À/À mice.…”

Identification of α-1L Adrenoceptor in Rabbit Ear Artery

“…However, the present study shows that both ␣-1L and ␣-1A ARs coexist in the intact tissue of rabbit ear artery. Recently, we have found that [ 3 H]KMD-3213 bound to only ␣-1A ARs in the intact segments of rat tail artery (I. Muramatsu, T. Tanaka, F. Suzuki, H. Yamamoto, Y. Hiraizumi-Hiraoka, and S. Morishima, unpublished data), where functional ␣-1A and ␣-1B ARs but not ␣-1L ARs have been demonstrated (Lachnit et al, 1997;Murata et al, 1999;Taki et al, 2004). Therefore, even though ␣-1A and ␣-1L ARs may be derived from the ␣-1L Adrenoceptor in Rabbit Ear Artery same gene, it is likely that both the subtypes are not necessarily expressed in parallel manner.…”

.ALPHA.-Adrenergic Receptor Mediated Hypertensive and Vasoconstrictor Effects of Dietary Radish Leaves Extract

“…17,18) The results show hypertensive and vasoconstrictor effects of the radish leaves crude extract on the blood pressure of rats and vascular tissues from rabbit, possibly mediated through activation of α-adrenergic receptors. The effect on blood pressure observed in rodents appears to be mediated at relatively large doses, however, in view of the fact that small animals like rats and mice are known to have a more rapid metabolism (around 10 times faster) than humans, 19) the dose in humans for the hypertensive effect might have been close to 30 mg/kg.…”