There are a large amount of data implicating the involvement of the sympathetic nervous system in the development or maintenance of hypertension. The 2-kidney deoxycorticosterone-acetate (DOCA) treated Yucatan miniature swine is a low renin model of hypertension which demonstrates increased total peripheral (TPR) and renal vascular resistance. Recent studies from this laboratory have shown that there are significant alterations in renal function in these hypertensive animals. Renal vascular resistance is elevated, sodium excretion is descreased, and these hypertensive animals are unable to maintain normal glomerular filtration rates or salt and water excretion when renal perfusion pressures are reduced to normal levels. We have also shown that alpha adrenergic receptor blockade significantly lowers arterial pressure via a selective decrease in TPR. Intrarenal alpha blockade increases renal blood flow and sodium excretion. We have also recently determined that circulating plasma norepinephrine is significantly elevated in DOCA animals when compared to controls. These findings support the hypothesis that sympathetic nerve activity is elevated in this hypertensive animal model. The major question being addressed by this project is whether renal sympathetic activity is elevated and/or important in these DOCA swine. Experiments are designed to directly measure renal nerve activity, evaluate the effects of surgical and pharmacological renal denervation, and to assess the effects of sympathetic ganglionic blockers and specific alpha-1 and alpha-2 receptor antagonists. We have obtained preliminary data indicating that acute renal denervation alters basal renal function in these animals. In the rat and dog that renal adrenergic activity may directly enhance renal tubular sodium reabsorption. The initial studies from this project suggest that this neurogenic effect also occurs in these swine. Experiments in the DOCA swine are designed to differentiate between the indirect renal hemodynamic and direct renal tubular influences that increased sympathetic activity may have on sodium excretion.
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