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 ®eld stimulation (1 ± 8 Hz) under di erent conditions, at 378C and during cooling (308C). 2 Electrical ®eld stimulation produced frequency-dependent contraction, which was reduced during cooling (about 60% for 8 Hz). Both at 378C and 308C, phentolamine (1 mM) or blockade of a 1 -adrenoceptors with prazosin (1 mM) reduced, whereas blockade of a 2 -adrenoceptors with yohimbine (1 mM) increased, the contraction to electrical ®eld stimulation. This contraction was increased after desensitization of P2-receptors with a,b-methylene adenosine 5'-triphosphate (a,b-meATP, 3 mM) at 378C but not at 308C, and was not modi®ed by blockade of P2-receptors with pyridoxalphosphate-6-azophenyl-2,4'-disulphonic acid (PPADS, 30 mM) at either temperature. 3 Endothelin-1 (1, 3 and 10 nM) at 378C did not a ect, but at 308C it potentiated in a concentrationdependent manner the contraction to electrical ®eld stimulation (from 28+6 to 134+22%, for 8 Hz). At 378C, endothelin-1 in the presence of phentolamine or prazosin, but not in that of yohimbine, a,bmeATP or PPADS, potentiated the contraction to electrical stimulation. At 308C, phentolamine or yohimbine reduced, prazosin or PPADS did not modify and a,b-meATP slightly increased the potentiation by endothelin-1 of the response to electrical stimulation. 4 The arterial contraction to ATP (2 mM) and the a 2 -adrenoceptor agonist BHT-920 (10 mM), but not that to (7)-noradrenaline (1 mM), was potentiated by endothelin-1 at both 378C and 308C. 5 These results in the rabbit central ear artery suggest that the sympathetic response: (a) at 378C, could be mediated mainly by activation of a 1 -adrenoceptors, with low participation of P2-receptors, (b) is diminished during cooling, probably by a reduction in the participation of a 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 a 2 -adrenoceptors and P2-receptors.

Effect of neuropeptide Y on the sympathetic contraction of the rabbit central ear artery during cooling

“…It has been suggested that both noradrenaline, acting on post-junctional α-adrenoceptors, and ATP, acting on post-junctional purinoceptors, could mediate the sympathetic vasoconstriction, and their relative importance in this vasoconstriction may vary depending on the vascular bed, the species and the stimulation parameters [20]. In ear arteries, in the absence of NPY at 37°C, the purinergic component of the sympathetic response may be very small, and the adrenergic component may predominate, because the sympathetic response was reduced by phentolamine but not by PPADS, which confirms previous studies from our laboratory [16]. The participation of these components in the small potentiating effect of NPY at 37°C is unclear, because separate blockade of α-adrenoceptors with phentolamine, or of purinoceptors with PPADS, did not reduce the potentiation by NPY.…”

Temperature modulates P2X receptor-mediated cardiovascular responses to muscle afferent activation

“…Also, P2 receptor-mediated guinea pig urinary bladder and vas deferens responses were augmented at lower temperatures and attenuated at higher temperatures (31). Of note, in these reports (4,31), the cooling temperature was Յ30°C. Moderate cooling (35°C) on the other hand did not potentiate P2X-mediated vasoconstriction (13).…”

“…For example, P2 receptor-mediated vasoconstriction was more prominent at lower temperature than that under "normal" temperature conditions (4). Also, P2 receptor-mediated guinea pig urinary bladder and vas deferens responses were augmented at lower temperatures and attenuated at higher temperatures (31).…”

Cooling‐induced contraction of the rat gastric fundus: Mediation via transient receptor potential (TRP) cation channel TRPM8 receptor and Rho‐kinase activation

“…Cooling has been shown to enhance adrenergically mediated contractions of cutaneous veins and arterioles 1-3 while relaxing conduit arteries precontracted with a variety of spasmogens. [4][5][6][7][8] Non-vascular smooth muscles contract in response to cooling and the contraction is inversely proportional to temperature. This has been demonstrated in the trachea, [9][10][11][12] urinary bladder 13 and, recently, in smooth muscles of the gastrointestinal tract.…”