DESCRIPTION (Applicant's abstract): Static and moderate dynamic exercise are known to increase heart rate, myocardial contractility, arterial blood pressure, breathing and muscle sympathetic nerve discharge. These effects, which are believed to increase the delivery of oxygen to metabolically active tissues (i.e., the exercising muscles), appear to be less in women than in men. This difference is often attributed to the effect of estrogen on neuronal function. Consequently, the aim of the experiments proposed in this application is to identify the effect of estrogen on "central command" and the muscle reflex, the two neural mechanisms responsible for evoking the autonomic responses to exercise. The proposed studies will be done in decerebrate unanesthetized female and male cats, which have been either ovariectomized or castrated, respectively two to four weeks prior to the experiment. In this preparation, the two neural mechanisms, central command and the muscle reflex, can be investigated separately without the influence of anesthesia. The effect of estrogen (i.e., 17-beta-estradiol) on the central command to exercise will be studied while the cats are paralyzed with vecuronium, and will be evoked by both electrical and chemical stimulation of the hypothalamic and mesencephalic locomotor regions. Motoneuron discharge to agonist and antagonist hindlimb muscles will be recorded. The criterion for elicitation of central command will be "fictive locomotion." Likewise, the effect of estrogen on the muscle reflex will be studied, but the cats will not be paralyzed. The muscle reflex will be evoked both while the hindlimb muscles are freely perfused and while they are ischemic. Dose response relationships for the effect of estrogen on both the cardiovascular and respiratory responses to central command and the muscle reflex will be determined. Moreover, studies will be extended to estrogen pretreatment with timed release pellets implanted into castrated male cats and ovariectomized females. In addition, the effect of microinjections of 17beta-estradiol into the hypothalamic and mesencephalic locomotor regions will be determined because preliminary data suggest that central command, but not the muscle reflex, is responsible for the estrogen-induced attenuation of the cardiovascular and ventilatory responses to exercise.