Regulation of adrenergic receptor number following chronic noradrenaline infusion in the rabbit
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The mean arterial blood pressure, heart rate and catecholamine levels were measured before commencing, and after 24 h and 10 days infusion. Circulating noradrenaline concentrations were elevated approximately 6-fold at 24 h and were sustained at these levels after 10 days administration of noradrenaline. There were no significant alterations in the blood pressure while a significant decrease in the heart rate was observed at 24 h.
Alpha2-adrenoceptor density was assessed using [3H]-yohimbine. A significant decrease in the number of alpha2-adrenoceptors in the kidney was observed following the 10 days infusion with noradrenaline. This down-regulation was in marked contrast to the lack of alteration in platelet alpha2-adrenoceptor number and the platelet alpha2-adrenoceptor mediated aggregatory response.
The density of beta-adrenoceptors in lymphocytes, heart and lung were quantified using (−)[125I] iodocyanopindolol (ICYP). The noradrenaline infusions caused significant reductions in beta-adrenoceptor number in the heart and lung (containing predominantly β1-adrenoceptors) but not in lymphocytes (possessing mainly β2-adrenoceptors). The KD-values (pM) for ICYP binding to heart and lung were also significantly decreased in the present studies.
It is concluded that, in this model, a moderate increase in circulating noradrenaline resulted in substantial decreases in alpha- and beta-adrenoceptor number but in a tissue and/or subtype selective manner.
Key wordsNoradrenaline infusion Adrenergic receptors Regulation
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