Functional crosstalk of prejunctional receptors on the modulation of noradrenaline release in mesenteric vessels: A differential study of artery and vein

The role of angiotensin II receptors, bradykinin receptors and β-adrenoceptors in the modulation of noradrenaline release and the influence of α2-autoinhibition in these effects was investigated in the mesenteric artery and vein. Rings of mesenteric vessels of male Wistar rats were labelled with [3H]-noradrenaline and the effects of modulators on tritium overflow evoked by 100 pulses at 2 Hz (marked α2-autoinhibition) and by 20 pulses at 50 Hz or 100 pulses at 2 Hz plus yohimbine (1 μM; reduced α2-autoinhibition) were evaluated. Angiotensin II and bradykinin enhanced noradrenaline release evoked by 100 pulses at 2 Hz, in a concentration-dependent manner, in both vessels. These effects were attenuated under conditions of reduced α2-autoinhibition. The attenuation was partially reversed by activation of adenosine A1 receptors in both vessels and by activation of P2Y receptors in the vein. Isoprenaline and the selective β2-adrenoceptor agonist formoterol enhanced tritium overflow independently of α2-autoinhibition in the vein. In the artery, the enhancement by formoterol was only observed under reduced α2-autoinhibition. Pharmacological characterization of the β-adrenoceptors indicated that in the artery the effect of isoprenaline was mediated by the β1-subtype under marked α2-autoinhibition and by the β2-subtype under reduced α2-autoinhibition whereas in the vein the effect was independent of α2-autoinhibition. The results indicate that α2-autoinhibition is a key determinant of the magnitude of facilitation caused by angiotensin II and bradykinin in both types of mesenteric vessels and regulates the effects mediated by β1-and β2-adrenoceptors which co-exist in the artery.