Persistence of PAR-2 vasodilation despite endothelial dysfunction in BPH/2 hypertensive mice.
This study investigated relaxation of vascular smooth muscle by acetylcholine, bradykinin and protease-activated receptor 2 (PAR-2) to characterise endothelial dysfunction in spontaneously hypertensive mice (BPH/2). We hypothesised that PAR-2 induced vasodilation would be preserved in BPH/2 despite the presence of hypertension and impaired vasodilator responses to acetylcholine and bradykinin. Mean arterial blood pressure (MAP), heart rate and locomotor activity were assessed in conscious mice over 24-h periods by radiotelemetry. Relaxation responses of small mesenteric arteries to acetylcholine, bradykinin and the PAR-2 agonist, 2-furoyl-LIGRLO-amide (2fly), were assessed using wire myographs. MAP and heart rate of BPH/2 were 15 and 18%, respectively, higher than in controls (BPN/3). BPH/2 also exhibited increased locomotor activity. Maximal relaxations of arteries by acetylcholine and bradykinin in BPH/2 were reduced by 25-50% relative to BPN/3. In contrast, relaxation responses to 2fly were only slightly (6%), albeit significantly, reduced. Sodium nitroprusside-induced relaxations were not different between strains. Treatment of BPH/2 arteries with inhibitors of calcium-activated K(+) channels was sufficient to block persistent 2fly- and residual ACh- and bradykinin-induced relaxations, whereas NO synthase inhibitor failed to inhibit these relaxations. In BPH/2 mice, vascular smooth muscle relaxation by PAR-2 is well preserved despite the presence of hypertension and impaired vasodilation responses to acetylcholine and bradykinin.
McGuire
John J
JJ
Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada. mcguire@mun.ca
Van Vliet
Bruce N
BN
Giménez
José
J
King
James C
JC
Halfyard
Sarah J
SJ
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001920:Bradykinin / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D008124:Locomotion / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D008817:Mice, Mutant Strains; D009599:Nitroprusside / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D044464:Receptor, PAR-2; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine; D001920:Bradykinin