1. The relationship between α-adrenoceptor number and response has been studied in rabbits under a range of physiological and pathological conditions.
2. The effects of irreversible α-adrenoceptor blockade, maturation, ageing, oestrogen treatment, adrenaline infusion, perinephritis hypertension and sinoaortic denervation on α-adrenoceptor number and response were examined.
3. α-Adrenoceptor number was measured by radioligand binding. [3H]Prazosin and [3H]clonidine were used as ligands to measure α1- and α2-adrenoceptor number in spleen and [3H]yohimbine to measure α2-adrenoceptor number on platelets. Responses in vivo were studied by examining the pressor responses to a range of α-adrenoceptor agonists. The functional response of platelets was examined in vitro by using the aggregatory response to adrenaline.
4. Reductions in α2-adrenoceptor ligand binding were consistently accompanied by equivalent reductions in α2-adrenoceptor-mediated responses. In contrast large reductions in [3H]prazosin binding were observed with little or no change in α1-adrenoceptor-mediated responses.
5. These results would be consistent with a large receptor reserve for α1-adrenoceptors but few if any spare α2-adrenoceptors in the vasculature or on platelets.
6. Increased responses to both α1- and α2-adrenoceptor agonists were observed in animals with sinoaortic denervation and to α1-adrenoceptor agonists in rabbits with perinephritis hypertension. These increases in response were not accompanied by increases in radioligand binding and may be related to alterations in the coupling of receptor activation to end-organ response.