Androgens raise venous and arterial adrenergic tone.

高血压的发展是性二态的。血压上升得更快，更高 在男性中的范围。虽然相当多的研究注意力都指向动脉循环，但有 目前对高血压静脉病变的研究相对较少。我们之前的工作表明， 在高血压的发展阶段，神经机制使静脉张力升高 自发性高血压大鼠，一种类似于人类高血压的动物模型。近期 数据表明，高血压对静脉和动脉的影响是不同的。因此，该项目将测试 雄激素增强动脉和静脉血管间室肾上腺素能张力的一般假设 通过不同的机制。具体目标我将讨论这种影响发生在 血管平滑肌。SPARTIC AIM II将评估去甲肾上腺素释放变化的作用 机械装置。特殊目的III将研究雄激素在中枢神经系统控制机制中的作用 交感神经系统从下丘脑流出。功能研究将在体内进行，并 在隔离的灌流血管床中。雄激素诱导的蛋白质和基因表达的变化将是 用Western印迹和实时RT-PCR方法进行检测。总而言之，我们希望这些研究表明 雄激素能增强静脉和动脉的肾上腺素能张力，但潜在的机制是不同的 在这两个血管隔间里。这些数据将扩大我们对性激素调节的理解。 血管功能和高血压的发生发展。高血压是一个重大的公共卫生问题， 是许多其他心血管疾病的危险因素。此外，在患者中，高血压控制得很差。 此外，体位性低血压是降压治疗的常见不良反应，意味着调节失调。 静脉功能。更好地了解高血压患者动静脉张力的控制因素 可能导致设计副作用较少的降压药

The development of hypertension is sexually dimorphic. Blood pressure rises more quickly and to a greater extent in males. While considerable research attention has been directed toward the arterial circulation, there has been relatively little investigation of venous changes in hypertension. Our previous work indicated that venous tone was elevated by neural mechanisms in the developmental stages of hypertension in the spontaneously hypertensive rat, an animal model of that resembles essential hypertension in humans. Recent data suggest that veins and arteries are affected differently by hypertension. Thus, this project will test the general hypothesis that androgens amplify adrenergic tone of the arterial and venous vascular compartments via different mechanisms. Specific aim I will address the possibility that this effect occurs at the level of vascular smooth muscle. Specific aim II will assess the role of changes in norepinephrine release mechanisms. Specific aim III will investigate the effects of androgens on CNS mechanisms controlling sympathetic nervous system outflow from the hypothalamus. Functional studies will be conducted in vivo and in isolated perfused vascular beds. Androgen induced changes in protein and gene expression will be assessed with Western blot and real time RT-PCR approaches. Collectively we expect these studies to show that androgens amplify adrenergic tone in veins and arteries but that the underlying mechanisms are different in these two vascular compartments. These data will expand our understanding of sex steroid modulation of vascular function and of hypertension development. Hypertension is a significant public health problem that is a risk factor for many other cardiovascular diseases. In addition, in patients hypertension is poorly controlled. Moreover, postural hypotension is common adverse effect of antihypertensive therapy, implying dysregulation of venous function. A better understanding the factors that control arterial and venous tone in hypertension may lead to design antihypertensive drugs with fewer adverse effects