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Inhibition of platelet accumulation by β1-adrenoceptor blockade in the thoracic aorta of rabbits subjected to experimental sympathetic activation

  • Experimental Pharmacology
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Summary

Arterial platelet adhesion is an initiating event in the thrombo-embolic complications of atherosclerosis and may also accelerate the development rate of atherosclerotic lesions. Psychosocial stress has been shown to accelerate atherogenesis in animals, an effect probably mediated via β-adrenoceptor activation. In view of the postulated roles of platelets and β-adrenoceptor activation in atherosclerosis development, we decided to test whether β blockade affects arterial platelet accumulation. We studied the accumulation of radioactivity from 111In-labelled platelets on the wall of the thoracic aorta of rabbits as a measure of platelet accumulation. During the exposure to the labelled platelets, the animals were also exposed to 3 hours of chloralose anesthesia. This is a reproducible model of experimental sympathetic activation, including β-adrenoceptor activation, which we used to amplify possible effects of β-blockade on platelet-vessel wall interaction. The effectiveness of the anesthesia in increasing sympathetic activity was verified by significant rises in mean arterial blood pressure (from 77 to 88 mmHg), heart rate (190 to 290 bpm), and plasma levels of norepinephrine (1.0 to 3.3 nM) and epinephrine (0.13 to 0.83 nM). In chloralose anesthetized rabbits, approximately 30×10-9% of the injected 111In accumulated in each square millimeter of intima at unbranched thoracic aorta. Platelet accumulation was significantly higher at arterial branching points, 70% higher at intercostal artery bifurcations, and 150% higher at coronary artery bifurcations than in unbranched aortic intima. Pretreatment with metoprolol in a dose resulting in “therapeutic” plasma levels significantly reduced platelet accumulation by 48% in unbranched aorta, 65% at intercostal, and 53% at coronary artery bifurcations. βblockade also significantly blunted the hemodynamic responses to the sympathetic activation. β blockers have previously been shown to have antiaggregatory properties ex vivo; this study showed that β blockade also can reduce accumulation of platelets or platelet-derived products on the vessel wall in vivo. The relevance of the antiplatelet effect of β blockade found is discussed with regard to previously described effects of β blockade on the development and complications of atherosclerosis.

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Authors and Affiliations

  1. Preclinical Research & Development, Cardiovascular Pharmacology, Astra Hässle AB, 431 83, Mölndal, Sweden

    Knut Pettersson & Harriet Björk

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  1. Knut Pettersson
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  2. Harriet Björk
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Pettersson, K., Björk, H. Inhibition of platelet accumulation by β1-adrenoceptor blockade in the thoracic aorta of rabbits subjected to experimental sympathetic activation. Cardiovasc Drug Ther 6, 505–511 (1992). https://doi.org/10.1007/BF00055609

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