Effects of chronic subcutaneous adminstered proteinase-activated receptor 2-activating peptide on vascular reactivity of aortas and blood pressures in mice

Hughes, Keon H. (2011) Effects of chronic subcutaneous adminstered proteinase-activated receptor 2-activating peptide on vascular reactivity of aortas and blood pressures in mice. Masters thesis, Memorial University of Newfoundland.

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Abstract

The acute in vivo effects of proteinase-activated receptor 2 activating peptides (PAR₂₋AP) are reported to include vascular inflammation and hypotension. We studied the time- (7 and 14 days) and dose-dependent (2 nmol/kg/min and 6 nmol/kg/min) effects of chronic subcutaneous infusion with a PAR₂₋AP, 2-furoyl-LIGRLO-NH₂ (2fly), in C57BL/6J (C57) mice and PAR₂₋deficient (PAR₂⁻/⁻) mice. In aortas from PAR₂₋AP treated C57 mice the relaxation curve generated by 2fly was rightwardly shifted relative to saline-treated C57 mice. At specific times and doses of PAR₂₋AP treatment in C57 mice, the maximal endothelium-dependent (acetylocholine) and -independent (nitroprusside) nitric oxide-mediated relaxations of aortas were less than in saline-treated C57. Aortic expression of proteins associated with PAR₂₋AP induced smooth muscle relaxation was not significantly different between mouse strains and treatment groups. In C57 mine, 24 h hemodynamics and locomotor activity measured by radiotelemetry throughout the infusion periods indicated that 2fly high dose treatment lowered arterial systolic and pulse pressures relative to the baseline period when compared to saline infusions We conclude that PAR₂₋AP administered chronically in vivo produced aortic dysfunction in C57 mice which was characterized by attenuated endothelium-dependent PAR₂, cholinergic, and endothelium-independent nitric oxide-mediated relaxations. In spite of the in vivo vascular dysfunction, high dose 2fly-treatment lowered the systolic and pulse blood pressures of C57 mice.

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