The major aim of the proposed research is to define the cellular and molecular mechanism by which atrial natriuretic peptide (ANP) inhibits hormone stimulated aldosterone production from the adrenal glomerulosa cell. ANP, via a distinct surface receptor, inhibits the rate of aldosterone secretion stimulated by angiotensin II, extracellular potassium and adrenocorticotrophic hormone (ACTH). The stimulatory action of each of these agonists is mediated by the activation of cellular protein kinases. Using freshly isolated cells from calf adrenals, we will determine: 1) If ANP changes the cellular steady state concentration of cyclic nucleotides (increasing cGMP, decreasing cAMP) and/or alters the state of cyclic nucleotide turnover. 2) If these signals of ANP action, modulate receptor linked signal transduction events initiated by AII, ACTH, potassium. 3) If ANP prevents the activation of cellular protein kinases or enhances the stimulation of cellular phosphoprotein phosphatases. These studies will detail the biochemical mechanism of ANP action in the adrenal cell and as such, will help to realize the potential of ANP as a drug to be used in managing disorders of salt and water metabolism and in treating hypertension.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Experimental Cardiovascular Sciences Study Section (ECS)
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Yale University
Schools of Medicine
New Haven
United States
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