The role of the sympathetic nervous system (SNS) in long-term control of sodium excretion and arterial pressure is poorly understood. Nonetheless, it is recognized that increased sympathetic activity plays a role in the pathogenesis of salt and water retention in chronic sodium-retaining states including congestive heart failure, hepatic cirrhosis, and nephrotic syndrome, and in some forms of hypertension. Although the afferent mechanisms which mediate increased sympathetic activity in these disease states have not been established, baroreflex dysfunction is often an associated finding and has been hypothesized to account for chronic sympathoexcitation. In recent studies, we have found that chronic increments in salt intake and chronic angiotensin II (ANG II)- hypertension lead to sustained suppression of renal sympathetic activity (RSA) that promotes sodium excretion, suggesting that the SNS may contribute to long-term regulation of sodium balance and arterial pressure. The proposed studies will determine the afferent mechanisms which account for sustained inhibition of RSA during chronic increments in salt intake and chronic ANG II-hypertension, with particular emphasis on cardiopulmonary reflexes, which are especially important in suppressing RSA and promoting sodium excretion during acute increments in body fluids volumes. Another important goal will be to determine whether abolition of both sinoaortic and cardiopulmonary reflexes leads to salt-sensitive hypertension and exacerbation of ANG II-hypertension. To avoid extrapolating the finds from acute manipulations of the SNS to the chronic state, multiple techniques will be used in chronically instrumented dogs to directly examine the temporal effects of the renal sympathetic nerves on sodium excretion. These techniques include measurement of renal norepinephrine spillover as an index of changes in RSA and use of the split bladder preparations with permits simultaneous 24-h urine collection from an intact and denervated kidney. Additionally, alterations in afferent input into the central nervous system will be achieved by deafferentation of sinoaortic baroreceptors and cardiopulmonary receptors, and by control of plasma levels of ANG II. Thus, the proposed studies will directly test the hypothesis that neural-and/or hormonal-mediated renal sympathoinhibition is importantly involved in the chronic feedback regulation of body fluid volumes and arterial pressure under normal conditions and in hypertension.
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