A COMPARISON OF THE EFFECTS OF ANGIOTENSIN-II AND BAY K-8644 ON RESPONSES TO NORADRENALINE MEDIATED VIA POSTJUNCTIONAL ALPHA-1-ADRENOCEPTORS AND ALPHA-2-ADRENOCEPTORS IN RABBIT ISOLATED BLOOD-VESSELS

1 The effects of angiotensin II (AII) and Bay K 8644 on responses to noradrenaline (NA) mediated via postjunctional alpha-1- and/or alpha-2-adrenoceptors have been compared in three isolated venous preparations from the rabbit, the lateral sapheous vein, the left renal vein and the ear vein. 2 A similar action of AII and Bay K 8644 was observed only in the lateral saphenous vein; each potentiated responses to NA after isolation of a homogeneous population of postjunctional alpha-2-adrenoceptors. However, even in this preparation the mechanism of action for these agents was not identical. The sensitivity of KCl-induced contraction to changes in extracellular calcium ions (reflecting activation of voltage-dependent Ca2+ channels) was enhanced by Bay K 8644 but reduced by AII. 3 AII produced a selective facilitation of responses mediated via postjunctional alpha-2-adrenoceptors. In the lateral saphenous vein it reduced the effectiveness of prazosin an facilitated responses after isolation of alpha-2-adrenoceptors with phenoxybenzamine and rauwolscine. It directly enhanced response to NA in the ear vein, where only alpha-2-adrenoceptors are involved. In contrast, AII did not influence responses mediated via postjunctional alpha-1-adrenoceptors in the left renal vein (even after the receptor reserve had been removed with phenoxybenzamine) nor the 'rauwolscine-resistant' component of responses to NA in the saphenous vein. 4 Bay K 8644 enhanced contractile responses to NA mediated both via alpha-2-adrenoceptors, in the lateral saphenous vein, and via alpha-1-adrenoceptors in the left renal vein. Thus, unlike angiotensin II, no preferential effect was apparent. 5 Bay K 8644 was inactive against responses to NA in the rabbit isolated ear vein. Since the sustained component of responses to NA in this preparation is dependent upon the influx of extracellular Ca2+, these observations suggest that the influx of Ca2+ stimulated by NA is mediated via receptor-operated (1,4-dihydropyridine-resistant) Ca2+ channels.