Opposing hemodynamic effects of substance P on pulmonary vasculature in rabbits.

Published

Journal Article

Substance P is a peptide implicated in the control of a variety of physiological processes. Although substance P-containing neurons impinge on the pulmonary vasculature, the effects of substance P on the pulmonary circulation have not been systematically investigated. Rabbits were anesthetized with methohexital sodium and paralyzed with pancuronium bromide. Injection of substance P (0.002-0.10 microgram/kg) in the vena cava produced dose-dependent pulmonary vasoconstriction and systemic vasodilation. Pulmonary arterial pressure reached a peak within 15-20 s and declined toward base line over 10 min. Aortic pressure fell rapidly, reaching minimum at 5-10 s. At higher doses cardiac output fell transiently, resulting in a 65% fall in pulmonary vascular conductance. If repeat substance P dosages were administered 15 min apart, there was no tachyphylaxis. Pulmonary vasoconstriction was inhibited by the cyclooxygenase blocker meclofenamate (10 mg/kg) and the thromboxane synthase inhibitor Dazmegrel (UK-38,485) (2 mg/kg). In contrast, vasoconstriction was enhanced by atropine (2 mg/kg). In Dazmegrel-treated animals in whom pulmonary vasoconstriction was established by epinephrine infusion, low doses of substance P produced vasodilation. Our findings indicate that substance P produces pulmonary vasoconstriction via prostaglandin (particularly thromboxane) generation and pulmonary vasodilation via activation of cholinergic pathways.

Full Text

Duke Authors

Cited Authors

  • Worthen, GS; Gumbay, RS; Tanaka, DT; Grunstein, MM

Published Date

  • October 1, 1985

Published In

Volume / Issue

  • 59 / 4

Start / End Page

  • 1098 - 1103

PubMed ID

  • 2414267

Pubmed Central ID

  • 2414267

International Standard Serial Number (ISSN)

  • 8750-7587

Digital Object Identifier (DOI)

  • 10.1152/jappl.1985.59.4.1098

Language

  • eng

Conference Location

  • United States