Investigation of the mechanism of action of prostaglandin synthesis inhibitors on renin and aldosterone secretion and sodium excretion.

Mean blood pressure (MBP) was found to be lower, while renal plasma flow (RPF), glomerular filtration rats (GFR), sodium excretion rate (U(Na)V), potassium excretion rate (U(k)V) and urinary prostaglandin E (PGE) concentration were higher in 15 normotensive subjects (15NS) compared with the values obtained in 15 essential hypertensive patients (15EHP) of the same mean age. After volume expansion of the 15HP with isotonic saline infusion, RPF, U(Na)V, U(k)V, urine volume (UV) and urinary PGE increased significantly while plasma renin activity (PRA) decreased significantly. Urinary aldosterone concentration and MBP decreased also but not significantly. After oral administration of 75 mg of indomethacin, in the same loaded group of 15 EHP, urinary PGE, urinary aldosterone and PRA decreased significantly while RPF, GRF, U(Na)V remained unaltered and MBP increased. When these values obtained in saline loaded and indomethacin treated 15EHP were compared to those obtained in the same group before volume expansion, it was found that RPF, U(NaV, U(k)V and UV were higher after indomethacin-saline administration while MBP, GRF and urinary PGE did not differ significantly and PRA and urinary aldosterone were significantly lower. These findings argue against the suggestion that PGE increases sodium reabsorption at the distal tubule and indicate that the unaltered sodium excretion rate in saline loaded and indomethacin treated unanaesthetized subjects, results from the simultaneous decrease of renomedullary PGE, Renin and aldosterone secretion.