Potentiation by neuropeptide Y of vasoconstriction in rat resistance arteries

Abstract

1 The effects of neuropeptide Y (NPY) on resistance arteries were investigated on 3rd generation mesenteric arterioles of the rat.2 Contractions were elicited by noradrenaline (NA), 5-hydroxytryptamine (5-1HT), prostaglandin F2, (PGF2j), depolarization (KCI substituted for NaCl) and by the calcium agonist Bay K 8644, in the absence and in the presence of NPY (100nM), a concentration which by itself did not induce vasoconstriction. 3 NPY produced a leftward shift of the concentration-response curves to the agonists and to KCl, without any alteration of maximal contractions. 4 NPY also potentiated contractions elicited by addition of CaCl2 to KCl-depolarized vessels, but its effect on calcium-induced contractions decreased with increasing KCl concentrations (from 20 to 100mM). 5 Calcium-induced contractions were inhibited by the calcium channel blocker nitrendipine, both in the presence and absence of NPY (100nM). NPY increased slightly (but significantly) the sensitivity to nitrendipine (the apparent KB increased from 2.9 x 10-1°M to 1.6 x 10-10 M). 6 The KCl concentration necessary for the maximal effect of Bay K 8644 was decreased in the presence of NPY, and the sensitivity to the calcium channel agonist was increased. 7 Elevating the KCI concentration in the bath from 5 to 20mM (which gives the same displacement to the left of the KCI concentration-effect curve seen in the presence of NPY) induced a parallel leftward shift of NA and 5-HT concentration-response curves. This shift was identical to the one induced by NPY on 5-HT-evoked contractions, but it was significantly smaller (P < 0.001) than the shift of the NA concentration-response curve observed in the presence of NPY. In the latter case, NPY enhanced more markedly the contractions induced by low NA concentrations (between 10-' and 3 x 10-8M) than those induced by high concentrations (up to 3 x 10-7M), thus giving a shallow concentration-response curve. 8 The results strongly suggest that NPY partially depolarizes the arterioles and induces an increase in calcium entry through voltage-dependent channels, thus enhancing contractions elicited by agonists or by KCI-depolarization. In addition, they support the view that another mechanism also plays a part in the potentiation by NPY of the effects of low concentrations of NA.

Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries

“…However, when applied at baseline tension NPY induced little contractions and submaximal concentrations of the peptide caused an average modest enhancement of the contractile responses to both stimulation of noradrenergic nerves and exogenous NA. The low magnitude of this potentiating effect is in contrast to that reported for NPY in small arteries from other vascular beds (Andriantsitohaina & Stoclet, 1988;Prieto et al,1991;1997b), but would be in accordance with the inconsistent constrictor effects found for NPY in penile erectile tissues (Hedlund & Andersson, 1985;Kirkeby et al, 1991).…”

Effects of neuropeptide Y and calcitonin gene‐related peptide on sheep coronary artery rings under oxygenated, hypoxic and simulated myocardial ischaemic conditions

“…In endothelium-denuded sheep coronary artery rings, simulated ischaemia causes a relaxation (Kwan et al, 1989c (Neild, 1987;Andriantsitohaina et al, 1988). However, in sheep coronary artery rings with endothelium intact under oxygenated conditions, contraction caused by the thromboxane mimetic U46619 was not affected by pretreatment with NPY.…”

“…CGRP is a potent coronary vasodilator (Holman et al, 1986;Franco-Cereceda & Lundberg, 1987) whereas NPY is a vasoconstrictor and enhances the response to various constrictor substances in isolated blood vessels (Edvinsson et al, 1984;Andriantsitohaina & Stoclet, 1988). The functional significance of the nerves containing these peptides in the heart is still unknown.…”

Regional heterogeneity in the contractile and potentiating effects of neuropeptide Y in rat isolated coronary arteries: modulatory action of the endothelium

“…Studies concerning the specific role of the endothelium in mediating the vascular effects of NPY seem to be contradictory; both endothelium-dependence (Daly & Hieble, 1987;Hieble et al, 1989) and endothelium-independence (Andriantsitohaina & Stoclet, 1988;Budai et al, 1989) have been described. The direct contractile effect of NPY on human skeletal and pig splenic arteries, both regarded as small arteries, occurs via an endothelium-independent mechanism (Pernow & Lundberg, 1988;Pernow, 1989), but coronary constriction may involve formation of a cyclo-oxygenase product (Martin & Patterson, 1989).…”

“…Although there is little information about the actions of NPY on resistance vessels (Owen & Taphorn, 1988;Andriantsitohaina & Stoclet, 1988), a correlation between the vascular effects of NPY and the diameter of the vessels has been proposed: it induces a stronger contraction in small arteries whereas the potentiation of the responses induced by other vasoconstrictors seems to be restricted to larger arteries where NPY has little or no direct contractile effect (Pernow, 1988;Franco-Cereceda, 1989).…”