In vivo receptor characterization of neuropeptide Y-induced effects in consecutive vascular sections of cat skeletal muscle

1 It has been suggested that the vasoconstrictor response to neuropeptide Y (NPY) is located in the microvessels and that it increases with reduced vessel diameter. The aim of the present study was to analyse quantitatively, on the cat gastrocnemius muscle preparation in vivo, the effects of NPY on total regional vascular resistance (R(T)) and its distribution to large-bore arterial resistance vessels (> 25 mu m; R(a,prox)), small arterioles (< 25 mu m; R(a,micro)) and the veins (R(v)). Associated effects on capillary pressure (P-c,P-v) and fluid exchange were also studied. 2 Close-arterially infused NPY (1-32 mu g kg(-1) min(-1)) caused a dose-dependent, slowly developing vasoconstriction in all three vascular sections, yet with a preferential action in the small arterioles. At 32 mu g kg(-1) min(-1), NPY raised R(T) by 133 +/- 22%, R(a,prox) by 94+/-15%, R(a,micro) by 277+/-104% and R(v) by 81+/-11%. However, the veins (ED(50) = 3.9+/-1.2 mu g kg(-1) min(-1)) were more sensitive to NPY than both large-bore arterial vessels (ED(50) = 7.7+/-1.6) and small arterioles (ED(50) = 7.0+/-1.4). NPY decreased P-c,P-v due to an increase in the pre-to post-capillary resistance ratio. 3 Close-arterial infusions of Pro(34)NPY and peptide YY evoked vasoconstrictor responses which did not differ from the response to NPY. In contrast, the Y-2-preferring C-terminal fragments: Ac-[Leu(28), Leu(31)]-NPY(24-36) and NPY(13-36) were without effect in the muscle vascular bed. The selective NPY Y-1 receptor antagonist BIBP3226 (100 mu g kg(-1) min(-1), i.a.) abolished the vascular response to NPY. 4 The present findings indicate that the vasoconstrictor response to NPY in skeletal muscle is preferentially located in the small arterioles and mediated via the Y-1 receptor and, further, that Y-2 and Y-3 receptors do not play a significant role in the vasoconstrictor response to NPY in cat skeletal muscle. BIBP3226 was found to be an effective NPY antagonist in vivo and to lack agonist activity.