This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Instantaneous changes in blood pressure, such as those produced by assuming the upright posture, are regulated to a large extent by the autonomic nervous system. Patients suffering from autonomic failure lose these buffering capacity and are unable to compensate for venous pooling associated with standing. The more severe patients faint every time they attempt standing, because of profound orthostatic hypotension. Of interest, our studies indicate that approximately 50% of these patients have supine hypertension, which is entirely accounted for by an increased in systemic vascular resistance even in patients with very low plasma norepinephrine and virtually undetectable plasma renin activity. Our main objective is to understand the factor(s) driving this increased vascular resistance. Our underlying hypothesis is that understanding the mechanisms hypertension in autonomic failure will contribute to our understanding of cardiovascular regulation in general,and human hypertension in particular.
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