The Effects of Chronic Administration of Adrenaline on the Function and Number of Adrenoceptors in the Rabbit

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Abstract
Chronic (10-day) intravenous infusions of adrenaline (0.05 μmol/kg/h) were given to rabbits via osmotic minipumps implanted at the femoral vein. Blood pressure, heart rate, and plasma catecholamine concentrations were measured five times during the period of infusion. Tenfold elevations in circulating adrenaline levels were achieved within 24 h of commencing infusion and maintained throughout the study. This increase in plasma adrenaline was not accompanied by significant changes in blood pressure or heart rate. Rabbits were killed after 10 days: blood was withdrawn for platelet aggregation studies. Kidney, heart, and lung were also collected and α2-adrenoceptor number on platelets and kidney measured using [3H]yohimbine. Beta adrenoceptors on platelets, lymphocytes, heart, and lung were quantified using [125I]iodocyanopindolol. Adrenaline infusion led to a significant reduction in platelet aggregation responses to adrenaline (0.001–100 μM), together with a decrease in α2-adrenoceptor number on platelets, but no significant decrease in kidney α2-adrenoceptors. A significant decrease in the density of β adrenoceptors on heart and lung membranes was observed with no reduction in platelet and lymphocyte β-adrenoceptor number. Thus adrenaline-induced down-regulation of adrenoceptors in the rabbit was dependent on the location and subtype of adrenoceptor.