NONADRENERGIC SYMPATHETIC VASCULAR CONTROL OF THE HUMAN FOREARM IN HYPERTENSION - POSSIBLE INVOLVEMENT OF NEUROPEPTIDE-Y

Animal experimental evidence suggests that neuropeptide Y (NPY) is coreleased with norepinephrine (NE) from sympathetic nerve endings and is involved in nonadrenergic neurogenic vascular control of skeletal muscle. We wished to determine whether these findings may be extended to humans. Forearm blood flow (venous occlusion plethysmography) and the regional overflows of NE and NPY-like immunoreactivity (NPY-LI) were studied at rest and during sympathetic nerve activation by lower body negative pressure (LBNP; - 10 mm Hg, 10 min) in 10 hypertensive men before and after local alpha-adrenergic blockade by a dose of phenoxybenzamine (60-mu-g x 100 ml-1 x min-1 for 60 min), which most markedly attenuated responses to exogenous NE; propranolol (10-mu-g x 100 ml-1 x min-1) was present throughout. Phenoxybenzamine increased forearm blood flow at rest (11.5 +/- 1.0 vs. 3.9 +/- 0.3 ml x 100 ml-1 x min-1; p < 0.001). LBNP-evoked reduction of forearm blood flow (37 +/- 2%, p < 0.001) was attenuated (p < 0.001) but not abolished (18 +/- 2%, p < 0.001) by phenoxybenzamine. LBNP increased the overflow of NE from 5.0 +/- 1.7 to 8.2 +/- 3.0 pmol x 100 ml-1 x min-1 (p < 0.05) and that of NPY-LI from -9.0 +/- 4.4 to 8.0 +/- 4.9 fmol x 100 ml-1 x min-1 (p < 0.05) after phenoxybenzamine; effects on the evoked overflows of NE and NPY-LI before phenoxybenzamine were slight. Prejunctional inhibitory alpha-adrenoceptors may thus modulate NPY release as well. Our results suggest that the proposed nonadrenergic component of sympathetic vascular control in human skeletal muscle may be related to NPY release.