Role of the purinergic and noradrenergic components in the potentiation by endothelin-1 of the sympathetic contraction of the rabbit central ear artery during cooling

1 To examine the role of the purinergic and noradrenergic components in the potentiation of endothelin-1 on the vascular response to sympathetic nerve stimulation, we recorded the isometric response of isolated segments, 2 mm long, from the rabbit central ear artery to electrical field stimulation (1-8 Hz) under different conditions, at 37 degrees C and during cooling (30 degrees C). 2 Electrical field stimulation produced frequency-dependent contraction, which was reduced during cooling (about 60% for 8 Hz). Both at 37 degrees C and 30 degrees C, phentolamine (1 mu M) or blockade of alpha(1)-adrenoceptors with prazosin (1 mu M) reduced, whereas blockade of alpha(2)-adrenoceptors with yohimbine (1 mu M) increased, the contraction to electrical field stimulation. This contraction was increased after desensitization of P2-receptors with alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP, 3 mu M) at 37 degrees C but not at 30 degrees C, and was not modified-by blockade of P2-receptors with pyridoxalphosphate-6-azophenyl-2,4'-disulphonic acid (PPADS, 30 mu M) at either temperature. 3 Endothelin-1 (1, 3 and 10 nM) at 37 degrees C did not affect, but at 30 degrees C it potentiated in a concentration-dependent manner the contraction to electrical field stimulation (from 28 +/- 6 to 134 +/- 22%, for 8 Hz). At 37 degrees C, endothelin-1 in the presence of phentolamine or prazosin, but not in that of yohimbine, alpha,beta-meATP or PPADS, potentiated the contraction to electrical stimulation. At 30 degrees C, phentolamine or yohimbine reduced, prazosin or PPADS did not modify and alpha,beta-meATP slightly increased the potentiation by endothelin-1 of the response to electrical stimulation. 4 The arterial contraction to ATP (2 mM) and the alpha(2)-adrenoceptor agonist BHT-920 (10 mu M), but not that to (-)-noradrenaline (1 mu M), was potentiated by endothelin-1 at both 37 degrees C and 30 degrees C. 5 These results in the rabbit central ear artery suggest that the sympathetic response: (a) at 37 degrees C, could be mediated mainly by activation of alpha(1)-adrenoceptors, with low participation of P2-receptors, (b) is diminished during cooling, probably by a reduction in the participation of alpha(1)-adrenoceptors, and in this condition the response could be mediated in part by P2-receptors, and (c) is potentiated by endothelin-1 during cooling, probably by increasing the response of both postjunctional alpha(2)-adrenoceptors and P2-receptors.