beta-adrenoceptor desensitization during the development of canine pacing-induced heart failure

1. The goal of this review is to emphasize four major points regarding the dev 2. Catecholamine desensitization occurs prior to the development of HF (i.e. after 1 day of rapid pacing, physiological responses to beta-adrenoceptor stimulation are depressed by over 50%, yet no evidence of HF is observed for 3-4 weeks of rapid pacing). 3. Multiple mechanisms in the beta-adrenoceptor cascade are involved. In HF there are decreases in beta(1)-adrenoceptors, high affinity beta-adrenoceptors, adenylyl cyclase activity and messenger RNA and increases in G(i). 4. Not all mechanisms appear simultaneously (i.e. early decreases occur in high affinity beta-adrenoceptors and adenylyl cyclase; late increases in G(i) and decreases in beta-adrenoceptor density evolves). 5. Mechanisms distal to cAMP generation also play a role (i.e. alterations in ryanodine receptor binding and excitation-contraction coupling also. occur).