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BACKGROUND Marked decreases in cardiac responses to beta-adrenergic stimuli have been found in cellular, animal, and human models of physiologic aging. As another probe of receptor-regulated cardiovascular changes with aging, responses to dopamine were studied. Responses were studied with and without depletion of myocardial catecholamines to eliminate effects secondary to myocardial catecholamine release. METHODS Responses of heart rate (A-A intervals), atrioventricular conduction (AV intervals and AV Wenckebach block cycle length) to 0-50 microM dopamine were studied in Langendorff perfused hearts from 10 mature (6.2 +/- 0.8 mo, mean +/- SD) and 9 senescent (23.6 +/- 0.7 mo) Fischer 344 rats and in hearts from 10 mature (5.3 +/- 0.4 mo) and 8 senescent (23.9 +/- 0.8) Fischer 344 rats after myocardial catecholamine depletion by reserpine (0.25 mg/kg i.p. x 5 days). RESULTS Dopamine decreased A-A (p < .0001) and AV conduction intervals (p < .0001) and increased peak developed pressure (p < .0001) and dP/dt (p < .001) in hearts from nonreserpine treated mature and senescent rats. Greater decreases in A-A intervals and AV conduction were seen in senescent compared to mature hearts (p < .0001). Contractile responses were greater in mature hearts (p < .001). After reserpine, A-A interval and paced AV conduction dose vs response relationships shifted rightward (p < .0001), but peak responses and age-related differences in responses were not significantly affected. In contrast, increases in peak developed pressure were greatly reduced in mature hearts (p < .0001) and age-related differences in contractile responses to dopamine were eliminated in hearts from reserpine-treated rats. CONCLUSIONS (a) A-A interval and AV conduction responses to dopamine were greater in senescent hearts even after catecholamine depletion, suggesting age-related differences in sinus and AV nodal responses to direct dopaminergic stimuli exist. (b) Age-related differences in contractile responses to dopamine were eliminated by reserpine suggesting basal age-related differences in response were secondary to age-related differences in responses to myocardial catecholamine release.

The sudden withdrawal of propranolol and atenolol was studied in five normal volunteers. Exercise testing was performed during the withdrawal period and physiological responsiveness compared to control responses. A significantly heightened reactivity of the blood pressure with early exercise was found after discontinuation of both drugs. A significant acceleration of the heart rale response with early exercise was seen only following propranolol withdrawal. When the combined effect (heart rate x systolic blood pressure) was analyzed, a significant increase in the double product achieved with low levels of exercise was observed following the sudden withdrawal of only propranolol administration.

Potential senescence-related effects of verapamil were studied in spontaneously beating isometrically contracting right atria from 12 mature and 9 senescent male Fischer 344 rats. Verapamil 0-300 mcg/L prolonged spontaneous cycle length in all atria but produced significantly greater prolongation of spontaneous cycle length in the senescent vs mature right atria (p less than .03). In addition, cessation of spontaneous activity occurred more frequently and at lower concentrations in senescent vs mature atria. Recovery times from pacing at 3.5 pps and 5.0 pps also showed greater prolongation in response to verapamil in the senescent atria when compared to the mature right atria (p less than .004 and p less than .002). In contrast, the percent reduction of developed force produced by verapamil during pacing at 3.5 and 5.0 pps did not differ between senescent and mature atria.