The objective of the proposed research is to investigate (1) the modulating influence of the renal nerves on renin secretion mediated by non-neural mechanisms and (2) the fundamental mechanisms which may be responsible for this modulating influence. In order to pursue these objectives, four specific questions have been posed: 1) Is the modulating influence of the renal nerves on renin secretion rate evident when the renal vascular receptor but not the macula densa is functioning? In non-filtering kidneys, changes in renin secretion rate will be determined for perfusion pressures greater than or equal to 40 mmHg before and during low level stimulation of the decentralized renal nerve bundle (0.25 Hz, 1 msec, 10 V). 2) Is the modulating influence of the renal nerves during aortic constriction evident in the autoregulatory range of renal perfusion pressures? Changes in renin secretion rate in filtering kidneys will be determined during reductions in renal perfusion pressure exclusively within the autoregulatory range for renal blood flow before and during low level renal nerve stimulation. Do the renal nerves sensitize the vascular receptor to small changes in pressure in the range of renal perfusion pressure in which GFR is also auto-regulated (greater than or equal to 100 mmHg)? Experiments will be performed in filtering and non-filtering kidney as described above. 3) Is the modulating influence of renal nerves mediated through alpha or beta adrenergic receptors? In filtering and non-filtering kidneys the renin secretion rate responses to aortic constriction and low level renal nerve stimulation will be examined before and after alpha adrenergic blockade. Also, the renin secretion rate responses to aortic constriction will be studied during infusion of alpha or beta agonists at does which are just supra- and subthreshold for changes in basal levels of measured variables. 4) Do prostaglandins participate in the neural modulation of non-neurally mediated renin release? In filtering and non-filtering kidneys the renin responses to aortic constriction and furosemide will be examined during low level renal nerve stimulation before and after arachidonic acid and before and after blockade of prostaglandin synthetase with indomethacin or meclofenamate (infused into renal artery).