CARDIOVASCULAR EFFECTS OF SPINAL-CORD SUBSTANCE-P - STUDIES WITH A STABLE RECEPTOR AGONIST

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 233  (3) , 755-760
Abstract
The role of spinal cord substance P (SP) in regulating sympathetic outflow to the cardiovascular system was assessed with the stable active analog [pGlu5, MePhE8, MeGly9]-SP(5-11) (DiME-SP). The interaction of DiME-SP with spinal cord SP receptors was evaluated initially in binding studies. Saturable, high-affinity binding of [125I]Bolton-Hunter-SP to rat spinal cord membranes was dose-dependently inhibited by DiME-SP (IC50 [concentration giving 50% inhibitor] = 1.5 .mu.M). Intrathecal (i.t.) injections of DiME-SP (1.0-33 nmol) in anesthetized rats produced dose-dependent increases in blood pressure and heart rate that were accompanied by increases in plasma epinephrine and norepinephrine. I.v. injections of the ganglionic blocker pentolinium blocked the cardiovascular and plasma catecholamine responses to i.t. injections of DiME-SP. Bulbospinal sympathoexcitatory pathways originating in the ventral medulla and their mediation by SP were also assessed. Application of bicuculline, the GABA receptor antagonist, to the ventral surface of the medulla produced sympathetic mediated increases in blood pressure and these effects were blocked by i.t. injection of the SP receptor antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP. The specificity of the SP antagonist for SP receptors was studied by attempting to alter the actions of the SP antagonist with a SP agonist. Administration of DiME-SP (33 nmol i.t.) blocked the effects of [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP (3.3 nmol i.t.). Specifically, the SP agonist countered the SP antagonist-mediated hypotensive response and inhibitory effect on bicuculline-induced sympathoexcitatory responses elicited from the ventral surface of the medulla. SP apparently transmits excitatory information to the cardiovascular system via spinal sympathetic pathways.