Androgens raise venous and arterial adrenergic tone.

高血压的发展具有性别二态性。血压升高得更快， 男性的程度。虽然相当多的研究注意力已经指向动脉循环， 对高血压静脉变化的研究相对较少。我们以前的工作表明， 静脉张力升高的神经机制，在发展阶段的高血压， 自发性高血压大鼠，一种类似于人类原发性高血压动物模型。最近 数据表明，静脉和动脉受高血压的影响不同。因此，该项目将测试 雄激素增强动脉和静脉血管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以下层面的可能性： 血管平滑肌具体目标II将评估去甲肾上腺素释放变化的作用 机制等具体目标III将研究雄激素对中枢神经系统机制的影响， 交感神经系统从下丘脑流出。将在体内进行功能研究， 在隔离的灌注血管床中。雄激素诱导的蛋白质和基因表达的变化将是 用Western blot和真实的实时RT-PCR方法进行评估。总的来说，我们希望这些研究表明， 雄激素增强了静脉和动脉中的肾上腺素能张力，但其潜在机制不同， 在这两个血管间室。这些数据将扩大我们对性类固醇调节的理解， 血管功能和高血压的发展。高血压是一个重要的公共卫生问题， 是许多其他心血管疾病的危险因素。此外，患者的高血压控制不佳。 此外，体位性低血压是降压治疗的常见不良反应，意味着失调 静脉功能。更好地理解控制高血压动脉和静脉张力的因素 可能导致设计副作用更少的抗高血压药物

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