Vasomotor Mechanisms in the Human Cutaneous Circulation

描述(申请人提供)：皮肤循环是最易变的之一，有可能产生非常高水平的血液流动。它的控制对体温调节以及一般的血流动力学和血压调节都是重要的。人类的这种控制机制正在变得清晰起来。在实验室的近代史上，我们有了几个重要的发现。我们已经清楚地表明，在女性中，肾上腺素能血管收缩系统和非肾上腺素能活性血管扩张系统的控制都受到生殖激素状态的影响，当雌激素和孕激素升高时，体温及其控制被转移到更高的水平。我们还知道，皮肤循环的重要控制不仅来自温度调节反射，还来自压力感受性反射和与动态运动相关的反射，即非温度调节反射。第三，我们发现，交感血管收缩控制和皮肤循环的主动血管扩张控制都有初级递质和辅助递质参与其血管舒缩功能。我们有强有力的证据表明，NPY在对身体降温的反射性血管收缩反应中具有重要的协同递质作用，VIP在对身体变暖的主动血管扩张反应中作为胆碱能协同递质具有重要作用。我们建议将这些控制因素结合在一起，试图发现月经周期中血管收缩控制的周期性变化是否通过交感神经共递质NPY；类似地，在血管扩张系统(VIP)中是否存在与激素相关的共递质角色的转变。我们还试图发现交感神经共同递质在非体温调节反射对皮肤血管控制的影响中的作用，特别是在运动开始时，在运动继续时抑制皮肤血流量增加以及当血压受到模拟出血的挑战时。最后，我们将测试除去甲肾上腺素和NPY I以外的交感神经递质的功能作用，NPY I是皮肤循环的血管收缩控制，特别强调ATP的潜在作用。

DESCRIPTION (provided by applicant): The cutaneous circulation is one of the most variable and has the potential for very high levels of blood flow. Its control is important both to temperature regulation and to hemodynamics and blood pressure regulation generally. The mechanisms for that control in humans are gaining clarity. In the recent history of the laboratory, we have made several important findings. We have shown clearly that, in women, control of both the adrenergic vasoconstrictor and the nonadrenergic active vasodilator systems are subject to modification by reproductive hormone status such that body temperature and its control are shifted to higher levels when estrogen and progesterone are elevated. We also know that important control of the cutaneous circulation derives not only from thermoregulatory reflexes, but also from baroreceptor reflexes and the reflexes associated with dynamic exercise, i.e., nonthermoregulatory reflexes. Third, we found that the sympathetic vasoconstrictor control and the active vasodilator control of the cutaneous circulation each have both primary transmitters and co-transmitters involved in their vasomotor functions. We have strong evidence that NPY has an important co-transmitter role in the reflex vasoconstrictor responses to body cooling and that VIP has an important role as a cholinergic co-transmitter in the active vasodilator response to body warming. We propose to draw these elements of control together, by seeking to discover whether the cyclic variation in vasoconstrictor control during the menstrual cycle is via the sympathetic co-transmitter NPY; similarly, whether there is a hormonally associated shift in the role for the co-transmitter in the vasodilator system (VIP). We also seek to discover the roles for sympathetic co-transmitters in the influence of nonthermoregulatory reflexes on cutaneous vascular control, specifically, in response to the onset of exercise, in the inhibition of the increase in skin blood flow as exercise continues and when blood pressure is challenged by simulated hemorrhage. Lastly, we will test for a functional role for sympathetic transmitters other than norepinephrine and NPY I the vasoconstrictor control of the cutaneous circulation, with particular emphasis on a potential role for ATP.