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Minimal α1- and α2-adrenoceptor-mediated coronary vasoconstriction in the anaesthetized swine

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Summary

α-Adrenoceptor-mediated coronary vasoconstriction contributes to the initiation and aggravation of experimental and clinical myocardial ischaemia. However, the extent of α1- and α2-adrenoceptor-mediated constriction has not been characterized in the porcine coronary circulation despite the frequent use of this experimental model.

Fifteen swine were anaesthetized with either α-chloralose, enflurane or isoflurane to determine the amount of α-adrenoceptor-mediated coronary constriction elicited by either the selective α1-adrenoceptor agonist methoxamine or the selective α2-adrenoceptor agonist azepexole. The left anterior descending coronary artery was cannulated and perfused by an external pump delivering constant blood flow from the carotid artery. Following bilateral cervical vagotomy and ß-adrenoceptor blockade with propranolol (2 mg kg−1), graded dosages of either one of the α-adrenoceptor agonists (9–45 μg kg−1 min−1) were infused into the coronary perfusion line while coronary arterial pressure (CAP) was measured through a distal side arm of the cannula to detect changes in coronary vascular resistance. Infusion of the α-adrenoceptor agonists was terminated when systemic arterial pressure increased. Sonomicrometers were used to measure anterior left ventricular wall thickening for the assessment of regional contractile function. During methoxamine infusion, no increase in vascular resistance was observed during α-chloralose, enflurane or isoflurane anaesthesia, whereas the infusion of azepexole increased CAP from 103 ± 31 mmHg to 120 ± 35 mmHg (α-chloralose), from 101 ± 16 mmHg to 122 ± 11 mmHg (enflurane) and from 84 ± 20 mmHg to 94 ± 19 mmHg (isoflurane), respectively. In four additional swine anaesthetized with enflurane, the intracoronary infusion of the full catecholamine agonist noradrenaline in the presence of propranolol (6 mg kg−1) increased CAP from 98 ± 10 to 105 ± 10 mmHg prior to an increase in regional left ventricular function or systemic arterial pressure.

These results indicate that there are no α1- and relatively little α2-adrenoceptor-mediated coronary constrictive effects in swine. Furthermore, neither α-adrenoceptor agonist produced any detectable change in regional myocardial contractile function, regardless of the anaesthesia used.

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Authors and Affiliations

  1. Abteilung für Pathophysiologie, Zentrum für Innere Medizin, Universität Essen, Hufelandstraße 55, 4300, Essen, Federal Republic of Germany

    Rainer Schulz, Ron J. Oudiz, Brian D. Guth & Gerd Heusch

  2. Seaweed Canyon Laboratory, Department of Medicine, University of California, 92093, San Diego, La Jolla, CA, USA

    Rainer Schulz, Ron J. Oudiz, Brian D. Guth & Gerd Heusch

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  1. Rainer Schulz
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  2. Ron J. Oudiz
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  3. Brian D. Guth
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  4. Gerd Heusch
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Supported by the German Research Foundation (He 1320/3-2). Dr. Guth is the recipient of a scholarship from the Alexander von Humboldt-Foundation.

Send offprint requests to G. Heusch at the above address

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Schulz, R., Oudiz, R.J., Guth, B.D. et al. Minimal α1- and α2-adrenoceptor-mediated coronary vasoconstriction in the anaesthetized swine. Naunyn-Schmiedeberg's Arch Pharmacol 342, 422–428 (1990). https://doi.org/10.1007/BF00169459

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