The kallikrein-kinin system and prostaglandins in the kidney: their relation to forosemide-induced diuresis and to the renin-angiotensin-aldosterone system in man.

Abstract

The relations among the renin-angiotensin-aldosterone system, renal prostaglandin E, the renal kallikrein-kinin system, and furosemide diuresis were studied in 16 healthy volunteers. The diuretic and natriuretic effects of furosemide were accompanied by an increase in the excretion rates of urinary prostaglandin E (UPCEV), urinary kallikrein (UkaiiV), and urinary kinin (U k i n i n V), and in plasma renin activity (PRA) and plasma aldosterone concentration (PAC). However, the time courses of the increase in PRA and PAC following furosemide administration and assumption of an upright posture were different from those of UPCEV, UkaiiV, UkininV, urine flow (UV), and urinary sodium output (UNBV). In comparison with the early increase in UPCEV, UkaiiV, UkininV, UV and UN O V, the increases in PRA and PAC were delayed. The augmentation of UPGEV, UkaiiV, and UkininV was closely related to the diuretic and natriuretic effects of furosemide. Highly significant correlations also were found between UPGE V and Ukaii V, UPGE V and Ukinin V, and Ukaii V and UkininV. On the contrary, there were no significant correlations between UPCEV and PRA or PAC, between Ukaii V and PRA or PAC, or between UkininV and PRA or PAC before and after the furosemide injection. These results indicate that the augmentation of urinary prostaglandin E and urinary kallikrein-kinin system following furosemide administration is independent of the renin-angiotensin-aldosterone system but directly dependent on the effects of furosemide. The possibility that renal prostaglandin E and the renal kallikrein-kinin system are involved in the diuretic and natriuretic effects of furosemide also is suggested by these experiments.