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Gender differences on the effects of aging on cardiac and peripheral adrenergic stimulation in old conscious monkeys

¹Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07101-1709; ²Simian Conservation Breeding and Research Center, Incorporated, Manila 1231; and ³St. Luke's Medical Center, Quezon City 1102, Philippines

Submitted 2 December 2002 ; accepted in final form 4 April 2003

We examined the effects of gender and aging on cardiac and peripheral hemodynamic responses to -adrenergic receptor (-AR) stimulation in young (male = 5.9 ± 0.4 yr old and female = 6.5 ± 0.7 yr old) and old (male = 19.8 ± 0.7 yr old and female = 21.2 ± 0.2 yr old) conscious monkeys (Macaca fascicularis), chronically instrumented for measurements of left ventricular (LV) and arterial pressures as well as cardiac output. Baseline LV pressure, the first derivative of LV pressure (LV dP/dt), cardiac index, mean arterial pressure, total peripheral resistance (TPR), and heart rate in conscious monkeys were not different among the four groups. Increases in LV dP/dt in response to 0.1 µg/kg isoproterenol (Iso) were diminished (P < 0.05) in old males (+99 ± 11%) compared with young males (+194 ± 18%). In addition, the inotropic responses to norepinephrine (NE) and forskolin (FSK) were significantly depressed (P < 0.05) in old males. Iso-induced reductions of TPR were less (P < 0.05) in old males (–28 ± 2%) than in young males (–49 ± 2%). The changes of TPR in response to NE and FSK were also significantly attenuated (P < 0.05) in old males. However, the LV dP/dt responses to BAY y 5959 (15 µg · kg^–1 · min^–1), a Ca²⁺ channel promotor independent of -AR signaling, were not significantly different between old and young males. In contrast to results in male monkeys, LV dP/dt and TPR responses to Iso, NE, and FSK in old females were similar to those observed in young females. Thus both cardiac contractile and peripheral vascular dynamic responses to -AR stimulation are preserved in old female but not old male monkeys. This may explain, in part, the reduced cardiovascular risk in the older female population.

sympathetic nerves; nonhuman primates; cardiac function; catecholamine desensitization; vascular function; adenosine 3',5'-cyclic monophosphate

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