DEPLETION OF ENDOGENOUS DOPAMINE STORES AND SHIFT IN BETA-ADRENOCEPTOR SUBTYPES IN CARDIAC TISSUE FOLLOWING 5 WEEKS OF CHRONIC DENERVATION

Surgical ablation of extrinsic cardiac nerve fibers results in a chron ically denervated state of the left ventricle of the heart. The presen t study was performed to elucidate the effect of a period of 5 weeks o f chronic denervation on cardiac catecholamine levels in general and d opamine in particular. Moreover, the possible effect on cardiac beta-a drenoceptor subtypes was investigated. Experiments were per-formed on adult dogs. In addition to adrenaline and noradrenaline the tissue lev els of dopamine were found to be severely depressed. A significant shi ft from beta 1- to beta 2-adrenoceptor subtype was observed, while the total beta-adrenoceptor density remained unaffected. The present find ings indicate that catecholamine synthesis in chronically denervated h earts is impaired upstream of dopamine and that a shift in beta-adreno ceptor subtype occurs already within a relatively short period of five weeks of denervation, and suggest that the lack of endogenous catecho lamines influence the relative expression levels of the two subtypes o f beta-adrenoceptors present in cardiac tissue.