Reflex control of the cutaneous circulation is both of thermoregulatory and of non-thermoregulatory origin and occurs via sympathetic vasoconstrictor and sympathetic active vasodilatory mechanisms. The applicant has previously shown that each of these 2 efferent systems is subject to control by internal temperature, skin temperature, exercise-associated reflexes, and baroreflexes. Steroidal changes accompanying the phases of the menstrual cycle are known to act as background modifiers of the thermoregulatory control of skin blood flow. The PI's working hypothesis is that in the luteal phase, progesterone inhibits active vasodilation by shifting to a higher internal temperature threshold for its initiation and elevates vasoconstrictor activity for any given body temperature as well. Elevated estrogen levels in the ovulatory phase are hypothesized to have directionally opposite effects on vasoconstriction and active vasodilator function. Through selective local blockade of vasoconstrictor function the applicant will examine changes in active vasodilator function among menstrual phases. Such effects would provide mechanisms for the well-documented phasic changes in basal internal temperature and in the control of the cutaneous circulation through the menstrual cycle. The applicant will also seek evidence for the roles of progesterone and estrogen in these phasic changes by taking advantage of the normal fluctuations of steroid levels among follicular (both low), ovulatory (estrogen elevated), and luteal (both elevated) phases to find how those hormonal patterns affect the control of the vasodilator and vasoconstrictor pathways. These studies will be complemented by examinations of alterations in control of the vasoconstrictor and vasodilator pathways between active and placebo phases of oral contraceptives. The applicant will evaluate peripheral contributions by these steroids in vasomotor function by testing whether vasoconstrictor responses to controlled application of norepinephrine or vasodilator responses to direct application of acetylcholine are dependent on the phase of the menstrual cycle. This question will be further addressed by finding if the level of skin blood flow in areas free of autonomic influences (via cutaneous nerve block) and in areas with intact innervation vary among phases of the menstrual cycle or between phases of oral contraceptive use. The role of prostaglandin synthesis in the upward shift of the thermoregulatory control of the active vasodilator system will also be evaluated.
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