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

Abstract

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°C and during cooling (30°C). 2. Electrical field stimulation produced frequency-dependent contraction, which was reduced during cooling (about 60% for 8 Hz). Both at 37°C and 30°C, phentolamine (1 μM) or blockade of α1-adrenoceptors with prazosin (1 μM) reduced, whereas blockade of α2-adrenoceptors with yohimbine (1 μM) increased the contraction to electrical field stimulation. This contraction was increased after desensitization of P2-receptors with α,β-methylene adenosine 5'-triphosphate (α,β-meATP, 3 μM) at 37°C modified by blockade of P2-receptors with pyridoxalphosphate-6-azophenyl-2,4'-disulphonic acid (PPADS, 30 μM) at either temperature. 3. Endothelin-1 (1, 3 and 10 nM) at 37°C did not affect, but at 30°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°C, endothelin-1 in the presence of phentolamine or prazosin, but not in that of yohimbine, α,β-meATP or PPADS, potentiated the contraction to electrical stimulation. At 30°C, phentolamine or yohimbine reduced, prazosin or PPADS did not modify and α,β-meATP slightly increased the potentiation by endothelin-1 of the response to electrical stimulation. 4. The arterial contraction to ATP (2 mM) and the α2-adrenoceptor agonist BHT-920 (10 μM), but not that to (-)-noradrenaline (1 μM), was potentiated by endothelin-1 at both 37°C and 30°C. 5. These results in the rabbit central ear artery suggest that the sympathetic response: (a) at 37°C, could be mediated mainly by activation of α1-adrenoceptors with low participation of P2-receptors, (b) is diminished during cooling, probably by a reduction in the participation of α1-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 α2-adrenoceptors and P2-receptors.