NEURAL RELEASE OF SUBSTANCE-P CAUSES DILATION OF ARTERIOLES IN RAT STRIATED-MUSCLE

Substance P, which is present in small nerve terminals and proximal to microvessels in rat strated muscle, may have a vasodilator role if released into the microcirculation. Male, Sprague-Dawley rats were anesthetized with sodium pentobarbital (50 mg/kg, i.p.) and the cremaster muscle, with intact blood supply and innervation, was suspended in a bath containing a physiological salt solution. The major autonomic innervation to the cremaster (genito-femoral nerve) was isolated and its cut, distal end was stimulated (3-5 Hz, 2 ms, 10-20 V). Diameters of third order arterioles (14-23 microns) were measured by television microscopy. Stimulation after a 20-min pretreatment with the alpha-adrenergic receptor antagonist phentolamine (2.10(-5) M) unmasked a moderate vasodilation, which was attenuated by treatment with the substance P receptor antagonist [D-Arg1,D-Pro2, D-Trp7,9,Leu11]-substance P (1.10(-6) M). This neurogenic vasodilation was not sensitive to muscarinic receptor blockade by atropine (1.10(-4) M), but was partially blocked by the beta-adrenergic receptor antagonist propranolol (1.10(-5) M). These data suggest that the rat striated muscle microvasculature is innervated with nerves containing substance P, and the release of substance P from the nerve terminals causes arteriolar dilation.