Vascular Effects of Proteinase-Activated Receptor 2 Agonist Peptide

• Published in: Journal of vascular research Vol. 34; no. 4; pp. 267 - 272
• Main Authors: Emilsson, Kjell, Wahlestedt, Claes, Sun, Miao-kun, Nystedt, Sverker, Owman, Christer, Sundelin, Johan
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.07.1997; S. Karger AG
• Subjects: Amino Acid Sequence; Animals; Antihypertensive Agents; Biological and medical sciences; Blood Pressure - drug effects; Blood vessels and receptors; Cardiac and Cardiovascular Systems; Clinical Medicine; Fundamental and applied biological sciences. Psychology; Heart Rate - drug effects; In Vitro Techniques; Kardiologi; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Molecular Sequence Data; Nitric Oxide Synthase - antagonists & inhibitors; Peptide Fragments - chemistry; Peptides - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, PAR-2; Receptors, Cell Surface - agonists; Receptors, Cell Surface - physiology; Research Paper; Vasodilation - drug effects; Vertebrates: cardiovascular system; Vascular endothelium; Proteinase-activated receptor 2; Nitric oxide; Hypotension; Vasodilation; Rat; Enzyme; Rodentia; Endothelium; Peptidases; Vasomotricity; Vertebrata; Membrane receptor; Mammalia; Arterial hypotension; Blood vessel; Hydrolases; Blood pressure; Circulatory system; Hemodynamics
• ISSN: 1018-1172; 1423-0135; 1423-0135
• DOI: 10.1159/000159233

Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled receptor related to the thrombin receptor. PAR-2 can be activated by trypsin and by synthetic peptides corresponding to the new amino terminus generated by activating proteolytic cleavage. We show in this report that intravenous injection of PAR-2 agonist peptides has dramatic effects on arterial blood pressure in anesthetized rats. The peptide SLIGRLETQPPI, at 150 nmol/kg, transiently decreased the mean arterial pressure from 104 to 60 mm Hg. The hypotensive response was dose-dependent, and was not secondary to effects on central vasoregulatory systems, heart rate, or the kidneys. A nitric oxide synthase inhibitor attenuated the hypotensive response induced by the PAR-2 agonist peptide. Further experiments in vitro, on preparations of rat femoral artery and vein, showed that PAR-2 agonist peptide elicited a dose-dependent relaxation of both types of vessel. Removal of the endothelium abolished the agonist peptide-induced relaxation. Our results demonstrate that activation of PAR-2 can modulate vascular tone, and that this response was an effect mediated at least partly by nitric oxide. The effect on blood vessels further suggests that the physiological activator of this proteolytically activated receptor is an enzyme present and active in the blood, possibly after a vascular injury.