Neuropeptide Y-induced potentiation of noradrenergic vasoconstriction in the human saphenous vein: involvement of endothelium generated thromboxane
- PMID: 9630349
- PMCID: PMC1565367
- DOI: 10.1038/sj.bjp.0701808
Neuropeptide Y-induced potentiation of noradrenergic vasoconstriction in the human saphenous vein: involvement of endothelium generated thromboxane
Abstract
1. We investigated the potentiating effect of low concentrations of neuropeptide Y (NPY) on the vasoconstriction induced by transmural nerve stimulation (TNS) and noradrenaline (NA) in human saphenous veins. The effects of (i) endothelium removal; (ii) the addition of the NO pathway precursor L-arginine; (iii) the ET(A)/ET(B) endothelin receptor antagonist Ro 47-0203; (iv) the cyclo-oxygenase inhibitor, indomethacin; (v) the selective thromboxane A2 (TxA2) receptor antagonists Bay u3405 and ifetroban, and (vi) the TxA2 synthase inhibitor, UK 38485, were studied in order to gain information about the mechanisms of NPY-induced potentiation. 2. Contractile response curves for TNS (0.5-8 Hz) and for exogenously administered NA (0.1-3 microM) were obtained in superfused saphenous vein rings. The contractions induced by both TNS and NA at all tested frequencies and concentrations, respectively, were significantly potentiated by 50 nM NPY in endothelium intact veins. Conversely, in endothelium-denuded vessel rings the contractile-response curves to TNS and NA overlapped both in the absence and presence of NPY, thus suggesting that a release of vasoactive substances from endothelial cells could account for the noradrenergic NPY-induced potentiation. 3. In vessels with intact endothelium, the potentiating action of NPY on TNS and NA was unaffected by the presence of high concentrations of the NO precursor L-arginine (3-10 mM) or the non-selective ET(A)/ET(B) endothelin receptor antagonist, Ro 47-0203 (10 microM). These data indicate that the NPY-induced effect does not involve either the endothelium-derived vasodilator nitric oxide or the vasoconstrictor endothelin. Conversely, in the presence of the cyclo-oxygenase inhibitor, indomethacin (30 microM), NPY failed to potentiate the vasoconstrictions produced by either nerve stimulation or by exogenous NA, thus providing evidence that arachidonic acid metabolites through the cyclo-oxygenase pathway are mainly responsible for the potentiation evoked by NPY. 4. When the TxA2 receptor antagonists, Bay u 3405 (1 microM) and ifetroban (1 microM) were added to the superfusing medium, NPY did not alter either the frequency- or the concentration-response curves for either TNS or NA. Accordingly, both TNS- and NA-induced contractions were not potentiated by NPY in the presence of the TxA2 synthase inhibitor, UK 38485 (10 microM). This clearly demonstrates the pivotal role of TxA2 in NPY-induced potentiation. 5. In superfused vein rings with endothelium, a subthreshold concentration (0.2 nM) of the TxA2 mimetic U 46619 potentiated both TNS- and NA-induced vasoconstrictions. This potentiation was higher at low stimulation frequencies and low NA concentrations, and resembled that produced by NPY. 6. Our results indicate that in the human saphenous vein NPY potentiates the contractions produced by sympathetic nerve stimulation acting at the postjunctional level, primarily on endothelial cells. In particular, the NPY-induced release of a cyclo-oxygenase metabolite, namely TxA2, may have a synergistic effect on the vasoconstriction induced by the noradrenergic mediator. Thus, such a mechanism may play a key role in the maintenance of the sympathetic tone of large human capacitance vessels.
Similar articles
-
Endothelium-dependent noradrenergic hyperresponsiveness induced by thapsigargin in human saphenous veins: role of thromboxane and calcium.Eur J Pharmacol. 2004 Jan 26;484(2-3):277-85. doi: 10.1016/j.ejphar.2003.11.017. Eur J Pharmacol. 2004. PMID: 14744614
-
[Neuropeptide Y contribution and the physiology of human sympathetic co-transmission. Studies in saphenous vein biopsies].Rev Med Chil. 2000 Aug;128(8):829-38. Rev Med Chil. 2000. PMID: 11129543 Review. Spanish.
-
Regional involvement of an endothelium-derived contractile factor in the vasoactive actions of neuropeptide Y in bovine isolated retinal arteries.Br J Pharmacol. 1995 Nov;116(6):2729-37. doi: 10.1111/j.1476-5381.1995.tb17234.x. Br J Pharmacol. 1995. PMID: 8590997 Free PMC article.
-
Effects of neuropeptide Y on the response of isolated blood vessels to norepinephrine and sympathetic field stimulation.J Pharmacol Exp Ther. 1989 Aug;250(2):523-8. J Pharmacol Exp Ther. 1989. PMID: 2668503
-
Effects of antihypertensive drugs on sympathetic vascular control in relation to neuropeptide Y.J Cardiovasc Pharmacol. 1987;10 Suppl 12:S51-68. J Cardiovasc Pharmacol. 1987. PMID: 2455193 Review.
Cited by
-
Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis.Front Cardiovasc Med. 2021 Feb 23;8:630968. doi: 10.3389/fcvm.2021.630968. eCollection 2021. Front Cardiovasc Med. 2021. PMID: 33708805 Free PMC article. Review.
-
Mechanisms of electrical vasoconstriction.J Neuroeng Rehabil. 2018 May 29;15(1):43. doi: 10.1186/s12984-018-0390-y. J Neuroeng Rehabil. 2018. PMID: 29843762 Free PMC article.
-
Role of the sympathetic autonomic nervous system in hypoxic remodeling of the fetal cerebral vasculature.J Cardiovasc Pharmacol. 2015 Apr;65(4):308-16. doi: 10.1097/FJC.0000000000000192. J Cardiovasc Pharmacol. 2015. PMID: 25853949 Free PMC article. Review.
-
Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction.Br J Pharmacol. 2012 Feb;165(3):591-602. doi: 10.1111/j.1476-5381.2011.01472.x. Br J Pharmacol. 2012. PMID: 21557734 Free PMC article. Review.
-
alpha(2)-adrenoceptor and NPY receptor-mediated contractions of porcine isolated blood vessels: evidence for involvement of the vascular endothelium.Br J Pharmacol. 1999 Dec;128(8):1705-12. doi: 10.1038/sj.bjp.0702979. Br J Pharmacol. 1999. PMID: 10588926 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous