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 neuropept ide Y (NPY) is located in the microvessels and that it increases with reduced vessel diameter. The aim of the present study was to analyse q uantitatively, on the cat gastrocnemius muscle preparation in vivo, th e 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 exchang e were also studied. 2 Close-arterially infused NPY (1-32 mu g kg(-1) min(-1)) caused a dose-dependent, slowly developing vasoconstriction i n all three vascular sections, yet with a preferential action in the s mall 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 rati o. 3 Close-arterial infusions of Pro(34)NPY and peptide YY evoked vaso constrictor responses which did not differ from the response to NPY. I n 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 vascu lar 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 pr esent findings indicate that the vasoconstrictor response to NPY in sk eletal muscle is preferentially located in the small arterioles and me diated via the Y-1 receptor and, further, that Y-2 and Y-3 receptors d o not play a significant role in the vasoconstrictor response to NPY i n cat skeletal muscle. BIBP3226 was found to be an effective NPY antag onist in vivo and to lack agonist activity.