FUNCTION OF THE PVN IN HEART FAILURE--ROLE OF NITRIC OXIDE AND GABA

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Patients with heart failure (HF) and all animal models of HF exhibit an increased sympathetic neural activation. This abnormality increases the risk of mortality during HF. The central mechanisms which underlie these abnormalities are poorly understood. We have recently obtained data which suggests that the paraventricular nucleus (PVN), a central sit known to receive afferent information from the heart and to alter sympathetic outflow, may contribute to the elevated neuro-humoral drive during the HF state. Furthermore, altered nitric oxide (NO) and gamma-amino butyric acid (GABA) mechanisms within the PVN may be involved in this sympatho-excitation. This proposal sets the hypothesis that disrupted NO and GABA mechanisms within the PVN contribute to the increased sympathetic drive in heart failure. We propose to: first, determine if No mechanisms within the PVN contribute to the increased sympathetic nerve activity in rats with HF; second, determine if GABA mechanisms within the PVN contribute to the increased sympathetic nerve activity in rats with HF; third, determine if there is altered interaction of NO and GABA mechanisms within the PVN in rats with HF; and fourth, determine if exercise training improves the altered NO and GABA mechanisms within the PVN in rats with HF. It is anticipated that No and GABA mechanisms within the PVN contribute to the sympathetic neural activation commonly observed during HF. The results should provide significant new information regarding central mechanisms of sympatho-excitation, specifically involvement of the NO and GABA systems within the PVN, in the increased sympathetic neural activation in the NF state. Understanding the role of central mechanisms not studied to date, in the increased sympathetic neural activation in the HF state. Understanding the role of central mechanisms, not studied to date, in the increased sympathetic neural drive would enhance our ability to treat HF condition and its cardiovascular complications.