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

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 EC₅₀ 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 [³H]-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.British Journal of Pharmacology (2004) 142, 647-656. doi:10.1038/sj.bjp.0705817 [ABSTRACT FROM AUTHOR]