title: Substance P induces a cardiovascular defense reaction in the rat: pharmacological characterization.
abstract: 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 alpha 1-adrenoceptor blockade with prazosin but were not influenced by blockade of vascular vasopressin receptors with d(CH2)5Tyr(Me) arginine vasopressin (AVP). Cardiac beta 1-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 beta 2-adrenoceptor blockade with ICI 118,551. Thus, the substance P-induced pressor effects are mediated by alpha 1-adrenergic sympathetic vasoconstriction and beta 1-adrenergic cardiac stimulation, whereas the hind limb vasodilation is mainly due to beta 2-adrenergic stimulation. Substance P dose-dependently (0.01-10 micrograms 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 classic cardiovascular defense reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Department of Pharmacology, University of Heidelberg, FRG.
authors: T
authors: T
authors: Unger
authors: S
authors: S
authors: Carolus
authors: G
authors: G
authors: Demmert
authors: D
authors: D
authors: Ganten
authors: R E
authors: RE
authors: Lang
authors: C
authors: C
authors: Maser-Gluth
authors: H
authors: H
authors: Steinberg
authors: R
authors: R
authors: Veelken
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects*; D003674:Defense Mechanisms; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D007276:Injections, Intraventricular; D008297:Male; D010907:Pituitary Hormones / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000494:pharmacology*; D014667:Vasopressins / Q000037:antagonists & inhibitors
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D010907:Pituitary Hormones; D014667:Vasopressins; D013373:Substance P; D001285:Atropine