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Acidosis Augments Myogenic Constriction in Rat Coronary Arteries

  • Published:
Annals of Vascular Surgery

Abstract

The myogenic response is a process by which blood vessels autoregulate vascular smooth muscle tone in response to changes in transmural pressure. It is characterized by vessel contraction or dilation with increased or decreased pressure, respectively. We sought to identify whether acidosis impacts the myogenic response in rat coronary resistance arteries. Ventricular septal arteries were isolated from male Sprague-Dawley rats and mounted on a pressure myograph. The myogenic response was assessed by measuring the arterial diameter at pressures of 10-120 mm Hg. The fluorescence indicators 2′,7′-bis-(carboxyethyl)-5(and-6)-carboxyfluorescein and Fura-2 were utilized to measure intracellular pH (pHi) and intracellular free calcium concentration ([Ca2+]i), respectively. A decrease in the extracellular pH (pHo) from 7.4 to 6.9 produced a fall in pHi and an increase in the myogenic response. Under nominally HCO −3 /CO2-free conditions at a constant pHo, blockade of the sodium-hydrogen exchanger with HOE694 also resulted in a fall in pHi and a similar enhancement of myogenic activity. Concentration response curves were constructed to measure the potencies of the HOE694 effects: the EC50 was 34 µM for the pHi change and 19 µM for vessel constriction. Apparent [Ca2+]i remained unchanged during HOE694-induced intracellular acidification. Furthermore, in the presence of HCO −3 , HOE694 did not markedly affect pHi and vascular tone remained unaltered. Our data demonstrate that acidosis augments myogenic constriction of rat coronary arteries. These effects are due to a fall in pHi consequent upon the reduction in pHo and may reflect an increased myofilament [Ca2+]i sensitivity within vascular smooth muscle cells.

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Acknowledgment

We thank Farzad Moien-Afshari and Claire Sheldon for their technical assistance with the experiments. Financial support was provided by grants to J. C. and I. L. from the Heart and Stroke Foundation of British Columbia and Yukon, Canada.

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Authors and Affiliations

  1. Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada

    Keith A. Baxter MD, FRCSC & York N. Hsiang MD, FRCSC

  2. Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada

    Ismail Laher PhD

  3. Department of Anatomy and Cell Biology, University of British Columbia, Vancouver, British Columbia, Canada

    John Church PhD

  4. Division of Vascular Surgery, Department of Surgery, University of British Columbia, 910 West 10th Avenue, Room 3100, V5Z 4E3, Vancouver, BC, Canada

    York N. Hsiang MD, FRCSC

Authors
  1. Keith A. Baxter MD, FRCSC
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  2. Ismail Laher PhD
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  3. John Church PhD
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  4. York N. Hsiang MD, FRCSC
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Corresponding author

Correspondence to York N. Hsiang MD, FRCSC.

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Baxter, K.A., Laher, I., Church, J. et al. Acidosis Augments Myogenic Constriction in Rat Coronary Arteries. Ann Vasc Surg 20, 630–637 (2006). https://doi.org/10.1007/s10016-006-9109-9

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  • DOI: https://doi.org/10.1007/s10016-006-9109-9

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