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 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 microM) or blockade of alpha(1)-adrenoceptors with prazosin (1 microM) reduced, whereas blockade of alpha(2)-adrenoceptors with yohimbine (1 microM) 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 microM) 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 microM) 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 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 microM), but not that to (-)-noradrenaline (1 microM), 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.