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Enhancement by neuropeptide Y (NPY) of the dihydropyridine‐sensitive component of the response to α 1 ‐adrenoceptor stimulation in rat isolated mesenteric arterioles
Author(s) -
Andriantsitohaina Ramaroson,
Stoclet Jean Claude
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14714.x
Subject(s) - phenylephrine , nitrendipine , prazosin , medicine , endocrinology , diltiazem , chemistry , vasoconstriction , neuropeptide y receptor , stimulation , calcium , neuropeptide , antagonist , receptor , blood pressure
1 The mechanism by which neuropeptide Y (NPY) potentiates the vasoconstriction induced by α 1 ‐adrenoceptor agonists was investigated in 3rd generation mesenteric arterioles of the rat. 2 At a maximally active concentration, nitrendipine (10 −6 m ) displaced to the right the concentration‐response curves to noradrenaline (pD 2 decreased from 6.2 ± 0.06 to 5.7 ± 0.03) and phenylephrine (pD 2 decreased from 5.6 ± 0.03 to 5.3 ± 0.03). Diltiazem (10 −5 m ) also shifted to the right the concentration‐response curve to phenylephrine (pD 2 decreased from 6.0 ± 0.06 to 5.5 ± 0.04). In addition, the maximal response to phenylephrine was significantly decreased in the presence of either nitrendipine or diltiazem. 3 In the absence of a calcium channel blocking agent, NPY (100 n m ) produced a leftward shift of the concentration‐response curves to noradrenaline (pD 2 increased from 6.2 ± 0.06 to 6.5 ± 0.05) and phenylephrine (pD 2 increased from 5.6 ± 0.03 to 6.0 ± 0.06 and from 6.0 ± 0.06 to 6.3 ± 0.11). In the presence of either nitrendipine (10 −6 m ) or diltiazem (10 −5 m ), NPY (100 n m ) did not alter the concentration‐response curves to either noradrenaline or phenylephrine. 4 NPY was added to arterioles brought to the same level of tension (40% of the maximal contraction) either by phenylephrine alone (1.5 × 10 −6 m ) or by a higher concentration of phenylephrine (3 × 10 −6 m ) followed by the addition of prazosin (1.3 × 10 −9 m ; a concentration at which it partially blocks α 1 ‐adrenoceptors). In these conditions, the response to phenylephrine was completely abolished by nitrendipine (10 −6 m ) or by diltiazem (10 −5 m ). Furthermore, NPY (10 −10 to 10 −7 m ) increased the arteriolar tension up to the maximal contractile capacity of the vessels with pD 2 values of 8.6 ± 0.02 and 8.7 ± 0.01, in the absence and presence of prazosin, respectively. 5 Prazosin was replaced in the above protocol by other vasodilator agents acting through different mechanisms. Whether in the presence of 2 × 10 −7 m forskolin, 6 × 10 −7 m sodium nitroprusside (which stimulate adenylate cyclase or guanylate cyclase, respectively) or 2 × 10 −7 m diltiazem (a concentration at which calcium entry is partially blocked), NPY enhanced phenylephrine‐induced contraction to the maximum level with an identical potency (pD 2 values of the peptide ranged from 8.3 to 8.7). 6 The results show that, in rat mesenteric arterioles, NPY potentiates only the calcium entry blocker‐sensitive component of contraction induced by stimulation of α 1 ‐adrenoceptors. In addition, they provide evidence that the peptide counteracts with an equal potency the inhibitory effect of partial block of α 1 ‐adrenoceptors and of relaxing agents acting through different mechanisms. It is suggested that NPY enhances calcium entry induced by stimulation of α 1 ‐adrenoceptors in this tissue.