Role of the renin-angiotensin system in prostaglandin E2-induced hypertension.

The effects of chronic (8 days) intrarenal protaglandin E, (PGE,) infusion on arterial pressure and renal function were assessed using unilaterally nephrectomized dogs maintained on a fixed sodium intake of 55 mEq/day.During 5 days of continuous intrarenal PGE, infusion (2 Mg/min) alone, both urine output and water intake increased markedly, and urine osmolality fell.Despite nearly a 9-fold increase in both plasma aldosterone concentration and plasma renin activity, daily sodium excretion exceeded intake values an average of 10-15 mEq/day, and plasma sodium concentration tended to fall.Concomitantly, arterial pressure increased from 104 ± 3 to 113 ± 2 nun Hg (p < 0.05) on Day 5. Infusion of saralasin (40 min) transiently lowered pressure from 112 ± 6 to 91 ± 7 mm Hg.PGE, was infused in combination with SQ 14,225 for 3 additional days, resulting in a fall in arterial pressure to * steady-state value of 82 ± 1 nun Hg.Concomitant with the fall in pressure, water and electrolyte excretion decreased during SQ 14,225 + PGE] infusion but, nonetheless, remained above control levels.In another group of dogs, continuous (6 days) intravenous infusion of prostaglandin F^,, at 25 Mg/min, had relatively moderate effects on water and electrolyte excretion and did not alter arterial pressure.Thus, it is unlikely that intrarenal conversion of PGE, to PGF 2a , with subsequent release into the systemic circulation, contributed to the PGE,-induced pressure rise.We conclude that chronic intrarenal PGE, infusion results in mild hypertension, which is dependent upon the renin-angiotensin system, and is associated with polyuria, polydipsia, and moderate natriuresis.(Hypertension 2: 529-537, 1980) KEY WORDS • prostaglandin E, • sodium and water balance • plasma renin activity arterial pressure • angiotensin blockade • prostaglandin F^ W E HAVE recently demonstrated that chronic (8 days) intrarenal prostaglandin E, (PGE,) infusion resulted in a 3-fold increase in urine output and moderate sodium loss. 1Despite a sustained diuresis and natriuresis, mean arterial pressure (MAP) increased 10-15 mm Hg, which was associated with a concomitant, 10-fold rise in plasma renin activity (PRA).The high degree of correlation (r = 0.96; p < 0.001) between the rise in PRA and MAP suggested that the mild hypertension observed during intrarenal PGE, infusion was causally related to the concurrent increase in PRA.Another mechanism, however, independent of the renin-angiotensin system, may have been operative during intrarenal PGE, infusion and have contributed to the observed increase in MAP.The enzyme PGE,-9-ketoreductase has been isolated from renal tissue of most species studied and catalyzes the conversion of PGEj to prostaglandin F,,,. 1 In contrast to PGE,-