The acute effect of lithium on renal renin and prostaglandin E synthesis in the dog.

Acute administration of lithium chloride (Li) to hydropenic anesthetized dogs significantly increased mean arterial pressure (MAP), plasma renin activity (PRA), and urinary prostaglandin E (UPGE) excretion with an increase in urinary volume, osmolar clearance, and sodium excretion. Solute-free water reabsorption increased during Li administration which argues against antagonism to ADH induced by increased PGE synthesis being a factor in the diuresis. The increase in renin secretion during Li administration was not caused by variation in sodium delivery to the macula densa, activation of the adrenergic nervous system, or change in renal resistance. Indomethacin, 5 mg/kg, prevented the rise in PRA and UPGE, abolished the natriuresis and diuresis, but did not prevent hypertension, whereas the angiotensin I-converting enzyme inhibitor, SQ20881, prevented both the rise in MAP and UPGE excretion. The fall in renal blood flow, rather than the inhibition of prostaglandin synthesis following indomethacin administration, probably accounted for the prevention of the natriuresis and diuresis since the converting enzyme inhibitor prevented the increase in UPGE excretion without effect on the natriuresis or diuresis. These studies demonstrate that Li increases renin and PGE synthesis. The increased renin secretion appears to be a direct effect of lithium on the juxtaglomerular apparatus, and the increase in PGE synthesis, which is secondary to angiotensin II generation, is not the cause of the diuresis or natriuresis. Circ Res 46: 739744, 1980