Adrenergic control of the cardiovascular system in deer mice native to high altitude

Abstract

Studies of animals native to high altitude can provide valuable insight into physiological mechanisms and evolution of performance in challenging environments. We investigated how mechanisms controlling cardiovascular function may have evolved in deer mice (Peromyscus maniculatus) native to high altitude. High-altitude deer mice and low-altitude white-footed mice (P. leucopus) were bred in captivity at sea level, and first-generation lab progeny were raised to adulthood and acclimated to normoxia or hypoxia. We then used pharmacological agents to examine the capacity for adrenergic receptor stimulation to modulate heart rate (f_H) and mean arterial pressure (P_mean) in anaesthetized mice, and used cardiac pressure-volume catheters to evaluate the contractility of the left ventricle. We found that highlanders had a consistently greater capacity to increase f_H via pharmacological stimulation of β₁-adrenergic receptors than lowlanders. Also, whereas hypoxia acclimation reduced the capacity for increasing P_mean in response to α-adrenergic stimulation in lowlanders, highlanders exhibited no plasticity in this capacity. These differences in highlanders may help augment cardiac output during locomotion or cold stress, and may preserve their capacity for α-mediated vasoconstriction to more effectively redistribute blood flow to active tissues. Highlanders did not exhibit any differences in some measures of cardiac contractility (maximum pressure derivative, dP/dt_max, or end-systolic elastance, E_es), but ejection fraction was highest in highlanders after hypoxia acclimation. Overall, our results suggest that evolved changes in sensitivity to adrenergic stimulation of cardiovascular function may help deer mice cope with the cold and hypoxic conditions at high altitude.