Substance P Induces a Cardiovascular Defense Reaction in the Rat: Pharmacological Characterization

In this study in conscious rats, we tested the hypothesis that substance P, a central pressor peptide and a potential transmitter substance of pain pathways, could be involved in the cardiovascular defense reaction that is typically associated with unpleasant sensory stimuli. The hemodynamic responses to centrally administered substance P were pharmacologically characterized. The increases in blood pressure and heart rate after intracerebroventricular injections of substance P were accompanied by mesenteric and renal vasoconstriction and hind limb vasodilation (pulsed-Doppler flow probes). The pressor and vasoconstrictor responses were attenuated by peripheral α1-adrenoceptor blockade with prazosin but were not influenced by blockade of vascular vasopressin receptors with d(CH2)5Tyr(Me) arginine vasopressin (AVP). Cardiac β1-adrenoceptor blockade with metoprolol abolished the tachycardic and reduced the pressor responses. Substance P-induced hind limb vasodilation was not sensitive to intravenous atropine but was largely prevented by peripheral β2-adrenoceptor blockade with ICI 118,551. Thus, the substance P-indnced pressor effects are mediated by α1-adrenergic sympathetic vasoconstriction and β1-adrenergic cardiac stimulation, whereas the hind limb vasodilation is mainly due to β2-adrenergic stimulation. Substance P dose-dependently (0.01–10 4mUg i.c.v.) released oxytocin but not vasopressin or adrenocorticotropic hormone (ACTH) from the pituitary gland. High doses reduced basal ACTH levels. Together with the hemodynamic responses, a behavioral arousal reaction was observed, which included increased locomotion, grooming, scratching, and skin biting. Our results demonstrate that a neuropeptide can induce a classic cardiovascular defense reaction. The endocrine component of the substance P-induced response (oxytocin release) is compatible with stress reactions, and the behavioral component is compatible with the reaction to nodceptive stimuli in rodents. We conclude that in the central nervous system, substance P may be important for the generation of an integrated cardiovascular and behavioral response pattern within the efferent pathways of the reaction to nociceptive stimuli.