Cardiac beta-adrenoceptor regulation and the effects of partial agonism.

The in vivo effects of xamoterol on the regulation of rat cardiac beta adrenoceptors were investigated. Rats were implanted subcutaneously with osmotic minipumps and exposed to the following treatment regimens: (1) subcutaneous infusion of saline (control), isoprenaline or xamoterol for 6 days, (2) subcutaneous infusion of isoprenaline with co-administration of xamoterol for various periods up to 96 hours, and (3) subcutaneous infusion of xamoterol for up to 96 hours after previous treatment with isoprenaline for 72 hours. Xamoterol did not induce beta-adrenoceptor down-regulation after short-term (72-hour) or long-term (6-day) infusions. When coadministered with isoprenaline xamoterol did not affect the rate or extent of down-regulation induced by isoprenaline alone. In addition, recovery of beta adrenoceptors down-regulated by isoprenaline treatment was not influenced by xamoterol treatment. In all studies, doses of xamoterol were equivalent to those producing full functional responses to the drug in vivo.