Endogenous prostaglandin biosynthesis powerfully influences renal function. Our preliminary studies indicate that renal production of prostaglandins (specifically PGE2) is progressively impaired with advancing age. This deficiency may be implicated in certain disturbances in renal function associated with aging, including an impaired ability to excrete water and to stimulate the secretion of renin and aldosterone. Common disorders of the elderly (especially elderly women) such as thiazide-induced hyponatremia and hyporeninemic hypoaldosteronism might therefore be related to prostaglandin metabolism. We will test this hypothesis by studying healthy young, middle-aged and old subjects as well as infirm elderly with a history of these disorders. All studies will be carried out in women to avoid contamination of urinary prostaglandins with prostatic secretions. The response of PGE2 excretion to physiological/pharmacological stimuli such as water diuresis, dietary challenge with unsaturated fatty acids and kininase inhibition will be examined and the effects on renal function noted. Parallel studies of the inhibition of prostaglandin synthesis, using indomethacin, will also be performed. Simultaneous measurements of the plasma levels of atrial natriuretic peptide, arginine vasopressin, renin/aldosterone, and endothelin will be made in many experiments, since these factors interact in their effects on the kidney and vascular system. The results should provide information about renal prostaglandin metabolism and its relationship to renal function in the elderly, clarify the pathophysiology of electrolyte disorders to which aged patients are predisposed, and suggest approaches to their prevention and therapy.
