SPINAL-CORD SEROTONIN RECEPTORS IN CARDIOVASCULAR REGULATION AND POTENTIATION OF THE PRESSOR-RESPONSE TO INTRATHECAL SUBSTANCE-P AFTER SEROTONIN DEPLETION

The aim of this study was to characterize, in conscious rats, the spin al cord 5-hydroxytryptamine (5-HT) receptors involved in mean arterial pressure (MAP) and heart rate (HR) regulation as well as to examine t he influence of bulbospinal 5-HT fibers on cardiovascular responses to intrathecal (i.t.) substance P (SP). The i.t. injection of 5-HT or 5- carboxamidotryptamine (5-CT) (5-HT1A,1B,1D agonist) reduced MAP and in creased HR in a dose-dependent manner. In contrast, the agonists 8-hyd roxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 5-HT1A agonist) and alph a-CH3-5-HT (5-HT1C and 5-HT2) only caused a decrease, in HR, while the agonist 2-CH3-5-HT (5-HT3) was devoid of cardiovascular effects. The vasodepressor response to 5-CT was antagonized by methiothepin but not affected by mesulergine, ketanserin, propranolol, or yohimbine. Howev er, all five antagonists reduced the HR increase to 5-CT. Ketanserin, propranolol, mesulergine, yohimbine, and methysergide were without eff ect on resting MAP, while methiothepin reduced MAP. Methiothepin, keta nserin, and methysergide increased resting HR, yet the other antagonis ts had no effect on this parameter. Rats treated with p-chlorophenylal anine or 5,7-dihydroxytryptamine, but not with 6-hydroxydopamine, exhi bited higher resting HR than that of control rats. Although the restin g MAP was unaffected, the pressor response to i.t. SP was significantl y enhanced by either 5-HT toxin. The results suggest that the receptor mediating the depressor response to 5-HT and 5-CT conforms with the b road pharmacological profile of a 5-HT1-like receptor and is unlikely to be of the 5-HT2 or 5-HT3 subtype. Since the HR response evoked by 5 -CT was blocked by antagonists that exhibit affinities for various 5-H T receptor subtypes, it is suggested that a nonspecific blockade or, a lternatively, that more than one receptor contributes to this cardiac effect. In addition, the results raise the possibility that a spinal 5 -HT input, likely mediated by 5-HT2 receptors, tonically inhibits HR. Hence, an antagonistic interaction between 5-HT and SP is proposed to play a role in the control of arterial blood pressure in the spinal co rd.