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Effects of acute pressure overload on prostacyclin release and myocardial blood flow in canine hearts: Inhibition of prostacyclin synthesis with 15-hydroperoxy-eicosatetraenoic acid

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Summary

This study was undertaken to evaluate the effects of acute pressure overload on prostacyclin (PGI2) release and the influences of 15-hydroperoxy-eicosatetraenoic acid (15-HPETE), an inhibitor of PGI2 synthetase, and indomethacin, an inhibitor of cyclo-oxygenase, in canine hearts. Gradual stenosis of the ascending aorta was performed in 24 anesthetized open-chest dogs. The mongrel dogs were divided into three groups, which received indomethacin, 15-HPETE, and no drug. Changes in the hemodynamics, regional myocardial blood flow (MBF) by the method of H2 gas clearance, and plasma immunoreactive 6-keto-prostaglandin (PG) F1α level in the descending aorta (AO) and great cardiac vein (GCV) were measured. Five minutes after aortic stenosis, the plasma immunoreactive 6-keto-PGF1α level in the GCV and MBF increased from 162±23 to 289±37 pg/ml and from 87±5 to 107±8 ml/min/100 g, respectively, and the calculated coronary vascular resistance (CVR) decreased significantly from 0.93±0.08 to 0.77±0.08 mmHg/ml/min/100 g. These significant changes persisted thereafter. Continuous infusion of 15-HPETE (66 pg/kg/min) into the coronary artery simultaneously prevented significant changes in MBF and the plasma immunoreactive 6-keto-PGF1α level in the GCV and CVR. Intravenous infusion of indomethacin (5 mg/kg), on the other hand, induced a significant decrease in the plasma immunoreactive 6-keto-PGF1α level in both the GCV and AO; significant changes in MBF 5 to 15 min after aortic stenosis and CVR were not affected. From these results, it is suggested that PGI2 plays an important role in the regulation of coronary blood flow in canine hearts with acute pressure overload. In addition, 15-HPETE rather than cyclo-oxygenase inhibitors was found to be beneficial in accurately determining the physiological activities of endogenous PGI2.

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Authors and Affiliations

  1. The 2nd Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, 466, Nagoya, Japan

    Masayuki Imaizumi, Yoshinobu Ito, Takayuki Ito, Kouichi Ogawa & Tatsuo Satake

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  1. Masayuki Imaizumi
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  2. Yoshinobu Ito
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  3. Takayuki Ito
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  4. Kouichi Ogawa
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  5. Tatsuo Satake
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Imaizumi, M., Ito, Y., Ito, T. et al. Effects of acute pressure overload on prostacyclin release and myocardial blood flow in canine hearts: Inhibition of prostacyclin synthesis with 15-hydroperoxy-eicosatetraenoic acid. Heart Vessels 3, 14–20 (1987). https://doi.org/10.1007/BF02073642

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  • DOI: https://doi.org/10.1007/BF02073642

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