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- Title
Effects of chronic in-vivo treatments with protease-activated receptor 2 agonist on endothelium function and blood pressures in mice.
- Authors
Hughes, Keon H.; Wijekoon, Enoka P.; Valcour, James E.; Chia, Elizabeth W.; McGuire, John J.
- Abstract
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.
- Subjects
PROTEASE-activated receptors; ENDOTHELIUM; BLOOD pressure; VASODILATION; RADIO telemetry; LABORATORY mice
- Publication
Canadian Journal of Physiology & Pharmacology, 2013, Vol 91, Issue 4, p295
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2012-0266