Enhancement by neuropeptide Y (NPY) of the dihydropyridine‐sensitive component of the response to α1‐adrenoceptor stimulation in rat isolated mesenteric arterioles

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Abstract
1 The mechanism by which neuropeptide Y (NPY) potentiates the vasoconstriction induced by α1-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 (pD2 decreased from 6.2 ± 0.06 to 5.7 ± 0.03) and phenylephrine (pD2 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 (pD2 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 nm) produced a leftward shift of the concentration-response curves to noradrenaline (pD2 increased from 6.2 ± 0.06 to 6.5 ± 0.05) and phenylephrine (pD2 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 nm) 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 α1-adrenoceptors). In these conditions, the response to phenylephrine was completely abolished by nitrendipine (10−6 m) or by diltiazem (10−5m). Furthermore, NPY (10−10 to 10−7 m) increased the arteriolar tension up to the maximal contractile capacity of the vessels with pD2 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 × 10−7m forskolin, 6 × 10−7m sodium nitroprusside (which stimulate adenylate cyclase or guanylate cyclase, respectively) or 2 × 10−7m diltiazem (a concentration at which calcium entry is partially blocked), NPY enhanced phenylephrine-induced contraction to the maximum level with an identical potency (pD2 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 α1-adrenoceptors. In addition, they provide evidence that the peptide counteracts with an equal potency the inhibitory effect of partial block of α1-adrenoceptors and of relaxing agents acting through different mechanisms. It is suggested that NPY enhances calcium entry induced by stimulation of α1-adrenoceptors in this tissue.