Project: Research project

Project Details


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.
Effective start/end date2/1/011/31/02


  • National Heart, Lung, and Blood Institute: $286,483.00

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