Principal Investigator: Mark Blumberg
Abstract: Recent work in the Principal Investigator's laboratory has shown that infant rats, contrary to a long-held view, exhibit many signs of successful thermoregulation when tested under appropriate conditions. Their success depends on the internal production of heat using brown adipose tissue (BAT), as well as the delivery of this heat to the heart. If BAT thermogenisis is not adequate and heart temperature decreases, cardiac rate decreases as well, resulting in significant challenges to the pup's ability to maintain arterial pressure and venous return to the heart. This application examines this thermoregulation-cardiovascular interaction in detail, and also addresses the hypothesis that the ultrasonic vocalizations emitted by infant and adult rats, typically assumed to be purposeful communicatory signals of emotional distress, are instead the acoustic by-products of a physiological maneuver that is recruited to maintain cardiovascular function during extreme cold exposure and in other physiologically challenging contexts. Aim 1 of this application addresses the neural and hormonal mechanisms by which infant rats increase peripheral resistance to the cold when cardiac output is decreasing. Specific mechanisms to be examined are alpha-1 adrenoreceptors, angiotensin II and vasopressin. Through selective blockade of each of these systems, as well as simultaneous blockade of all three systems, the interactions between cardiac rate, arterial pressure, venous return and ultrasound production are examined. Aim 2 addresses the proximate physiological stimuli that elicit ultrasound production and the associated changes in cardiovascular function that accompanies ultrasound production. For these experiments, venous return is (a) measured using Doppler flow probes and (b) manipulated using pharmacological and mechanical techniques. Finally, Aim 3 addresses the hypothesis that the infant and adult rat's ultrasonic vocalizations are homologous. This hypothesis, based on a variety of similarities between the two vocalizations is tested in adults by determining whether experimental decreases in venous return are sufficient to evoke ultrasonic vocalizations and by assessing cardiovascular changes during fever and copulation, two contexts associated with ultrasound production. This application addresses basic aspects of homeostatic regulation in infants and adults using behavioral, developmental, physiological approaches. Through these approaches, an integrated view of the varied mechanisms by which infant and adult mammals regulate cardiovascular function during physiological and behavioral challenges will emerge.
Funding Period: 2000-03-21 - 2004-02-28
more information: NIH RePORT