Short-term treatments with protease-activated receptor 2-activating peptides (PAR2-AP) induce endothelium-dependent vasodilation and decrease blood pressure. In this study, we tested the effect of chronic in-vivo treatment with PAR2-AP on the blood pressure and endothelium function
of mice. Male PAR2 wild-type (WT) and par2-deficient (KO) mice received subcutaneous infusions of either saline, low (PAR2-LD), or high (PAR2-HD) doses of 2-furoyl-LIGRLO-amide for 1 or 2 weeks. In each treatment group, endothelium function was assessed in isolated arteries. Blood pressure,
heart rate, and locomotor activity were recorded by radiotelemetry, and levels of tumour nercrosis factor α (TNF-α) and interkeukin 1β (IL-1β) were measured in plasma samples by ELISA. The relaxation of WT aortas and mesenteric arteries induced by PAR2-AP was decreased
by PAR2-LD and PAR2-HD. In mesenteric arteries, PAR2-LD and PAR2-HD decreased the relaxation induced by acetylcholine, but not by nitroprusside; in aortas, PAR2-LD and PAR2-HD caused differential decreases in the relaxations induced by acetylcholine and nitroprusside. Only PAR2-HD lowered
systolic arterial pressures in WT, when compared with all of the other groups. TNF-α and IL-1β plasma concentrations were not different among the groups. We conclude that the systolic blood pressure of unrestrained mice can be lowered by chronic in-vivo activation of PAR2; however,
this effect is countered by receptor desensitization and the concomitant development of endothelium and vascular dysfunction.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
protease-activated receptor 2;
Document Type: Research Article
Cardiovascular Research Group, Division of BioMedical Sciences, Memorial University, 300 Prince Philip Drive, St. John's, NL A1B 3V6, Canada.
Division of Community Health and Humanities, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL A1B 3V6, Canada.
Publication date: January 1, 2013
More about this publication?