Sympathetic postganglionic neurons that reside in the abdominal prevertebral ganglia provide vasoconstrictor control of the mesenteric vasculature. Changes in the function of the sympathetic innervation leads to changes in the vascular capacitance as well as the resistance of the mesenteric circulation and these changes modify systemic hemodynamics. The guiding hypothesis of this project is that changes in the properties of the sympathetic neurons that innervate veins contribute to the increase in blood pressure in some forms of hypertension. We hypothesize that venous sympathetic neurons are differentially susceptible to the factors that lead to increased blood pressure in DOCA salt rats. in the studies outlined in this project we will examine neurohumoral factors that function in neurovascular signaling by sympathetic neurons and how they are altered in hypertension. A combination of electrophysiologic, immunohistochemical and molecular biological techniques will be used to compare the properties of identified venous and arterial neurons in the prevertebral sympathetic ganglia of DOCA-salt hypertensive and SHAM rats. The studies consist of 4 specific aims. Specific Aim 1. Compare the properties of venous sympathetic neurons to those of arterial sympathetic neurons and other visceral neurons in normotensive SHAM and DOCA salt hypertensive rats. Specific Aim 2. Determine the localization and function of endothelin receptors on sympathetic neurons in normotensive SHAM and DOCA salt hypertensive rats. Specific Aim 3. Determine whether superoxide anion is elevated in sympathetic neurons of DOCA-salt hypertensive rats and whether this is due to an action of ET-1. Specific Aim 4. Compare the norepinephrine transporter message and expression and its modulation by endothelin and superoxide in venous and arterial sympathetic neurons from SHAM and DOCA-salt animals. Determining the pathophysiologic changes in the regulation of vascular sympathetic neurons in hypertension will provide the basis for the development of new strategies to understand and treat hypertension and other diseases of the cardiovascular system.
NIH ExPorter
NIH ExPorter