The research described in this application is intended to further explore humoral-hormonal modifiers of the functional expression of renal adrenergic activity at various effector loci in glomeruli, to characterize the nature of their influences, and to delineate the mechanisms involved.
The specific aims will be to determine the relative contributions of angiotensin II, renal prostanoids, and divalent cation calcium to the overall regulation of the process of glomerular ultrafiltration by the renal adrenergic nervous system. Studies utilizing in vivo micropuncture techniques and direct renal nerve stimulation will combine 1) the evaluation of glomerular hemodynamics, and 2) an analysis of net renal norepinephrine production, in an effort to ascertain the specific loci and modes of interactions, and to correlate functional responses and neuroeffector junction kinetics. In order to examine the functional role of the aforementioned factors, studies will systematically evaluate renal adrenergic effector mechanisms 1) in divergent states of endogenous angiotensin II activity, e.g., chronic dietary salt restriction or excess, 2) in a setting of renal prostanoids synthesis inhibition, i.e., cyclo-oxygenase or thromboxane synthetase inhibitors, and 3) during Ca++ entry blockers administration and in experimental conditions of negative or positive calcium balance. The central hypothesis set forth in this proposal is that the relative contribution of specific humoral-hormonal factors is a critical determinant of the functional expression of renal adrenergic activity in the renal microcirculation. It is hoped that these studies will provide valuable insights into the mechanisms of humoral-hormonal modulation of this important regulatory system of volume homeostasis.
