Inhibition of platelet accumulation by beta 1-adrenoceptor blockade in the thoracic aorta of rabbits subjected to experimental sympathetic activation.
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 beta-adrenoceptor activation. In view of the postulated roles of platelets and beta-adrenoceptor activation in atherosclerosis development, we decided to test whether beta 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 beta-adrenoceptor activation, which we used to amplify possible effects of beta-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 x 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Pettersson
K
K
Cardiovascular Pharmacology, Preclinical Research Development, Astra Hässle AB, Mölndal, Sweden.
Björk
H
H
D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology*; D001161:Arteriosclerosis / Q000209:etiology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002698:Chloralose / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D002698:Chloralose; D008790:Metoprolol