GLYCERYL NONIVAMIDE, A NONPUNGENT ANALOG OF CAPSAICIN, ENHANCES SUBSTANCE-P RELEASE AND RENAL-FUNCTION IN RATS

Effects of glyceryl nonivamide (GLNVA), a nonpungent analogue of capsa icin, on spinal substance P release, blood pressure and renal function were investigated in rats. GLNVA was administered intrathecally or in tracerebroventricularly, and renal clearance function was measured. Th e addition of GLNVA at concentrations of 2, 20 and 200 mu mol/l during in vivo spinal superfusion resulted in concentration-dependent increa ses in the release of sub stance P. Capsaicin pretreatment (50 mg/kg/d ay, s.c. for 2 weeks) blunted the GLNVA-induced substance P release, s uggesting a stimulation of GLNVA on the spinal terminals of capsaicin- sensitive primary afferent nerves to release substance P. Intracerebro ventricular administration of GLNVA at concentrations of 20, 40 and 80 nmol/l evoked a concentration-dependent depressor response. Despite t he hypotensive effect, GLNVA caused significant increases in glomerula r filtration rate, urine flow, absolute and fractional excretion of so dium and potassium, osmolar clearance and free water reabsorption rate . These data suggest that central administration of GLNVA stimulates s pinal substance P release, reduces blood pressure but enhances renal e xcretion of water and electrolytes due to an increased filtered load a nd a decreased tubular reabsorption.