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Persistence of PAR-2 vasodilation despite endothelial dysfunction in BPH/2 hypertensive mice

  • Cardiovascular System
  • Published:
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Abstract

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.

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Acknowledgement

This study was supported by grant funding to JJM from the Canadian Institutes of Health Research Regional Partnership Program, the Government of Newfoundland and Labrador Industrial Research and Innovation Fund, Canada Foundation for Innovation Ongoing New Opportunities Program and Memorial University.

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Authors and Affiliations

  1. Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John’s, Newfoundland, A1B 3V6, Canada

    John J. McGuire, Bruce N. Van Vliet, José Giménez, James C. King & Sarah J. Halfyard

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  1. John J. McGuire
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  2. Bruce N. Van Vliet
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  3. José Giménez
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  5. Sarah J. Halfyard
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Correspondence to John J. McGuire.

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McGuire, J.J., Van Vliet, B.N., Giménez, J. et al. Persistence of PAR-2 vasodilation despite endothelial dysfunction in BPH/2 hypertensive mice. Pflugers Arch - Eur J Physiol 454, 535–543 (2007). https://doi.org/10.1007/s00424-007-0226-2

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  • DOI: https://doi.org/10.1007/s00424-007-0226-2

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