Atrial natriuretic peptide(31-67) inhibits Na+ transport in rabbit inner medullary collecting duct cells. Role of prostaglandin E2.

Abstract

Atrial natriuretic peptide (ANP)(3l-7), a portion of the atrial peptide prohormone, circulates in humans, and its plasma level varies with atrial pressure. Like the more widely studied carboxy-terminal fragment ANP(,,26), ANP(3167)

Vessel Dilator Enhances Sodium and Water Excretion and Has Beneficial Hemodynamic Effects in Persons With Congestive Heart Failure

“…Vessel dilator is known to inhibit sodium reabsorption in the inner medullary collecting duct and renal tubules by inhibiting their Na ϩ -K ϩ -ATPases secondary to its ability to enhance the synthesis of prostaglandin E 2 , which appears to be the final mediator of the inhibition of renal Na ϩ -K ϩ -ATPase. 11,12 Thus, the ability of vessel dilator to inhibit renal Na ϩ -K ϩ -ATPase appears intact in persons with CHF on the basis of its ability to enhance the excretion of sodium and the filtration fraction of sodium. Furthermore, the decreased natriuresis and diuresis of experimental subject 5, who ingested a 325-mg aspirin tablet (which blocks prostaglandin E 2 synthesis) the night before the study compared with the other experimental subjects suggest that prostaglandin E 2 synthesis secondary to vessel dilator 11,12 is very important in mediating the effects of vessel dilator in persons with CHF.…”

“…11,12 Thus, the ability of vessel dilator to inhibit renal Na ϩ -K ϩ -ATPase appears intact in persons with CHF on the basis of its ability to enhance the excretion of sodium and the filtration fraction of sodium. Furthermore, the decreased natriuresis and diuresis of experimental subject 5, who ingested a 325-mg aspirin tablet (which blocks prostaglandin E 2 synthesis) the night before the study compared with the other experimental subjects suggest that prostaglandin E 2 synthesis secondary to vessel dilator 11,12 is very important in mediating the effects of vessel dilator in persons with CHF. Prostaglandin E 2 -mediated natriuresis appears to act at other nephron segments in addition to the inner medullary collecting duct, including the thick ascending limb, 18 and it is possible that vessel dilator also affects this portion of the nephron, although this has not been determined experimentally yet.…”

“…20 The ability of vessel dilator to retain its beneficial effects in CHF persons while the effects of atrial natriuretic factor become blunted appears to be due to the ability of vessel dilator to enhance prostaglandin E 2 synthesis in the kidney, which, in turn, inhibits renal Na ϩ -K ϩ -ATPase, resulting in a natriuresis. 11,12 Atrial natriuretic factor does not enhance the synthesis of prostaglandin E 2 or have the ability to inhibit renal Na ϩ -K ϩ -ATPase. 11,12 The natriuretic property of vessel dilator in CHF subjects is especially impressive in light of the facts that (1) the natriuretic effects of vessel dilator are not blunted in CHF as found in the present investigation and (2) the natriuretic and diuretic effects of vessel dilator are at least equal to atrial natriuretic factor, 1 which has been found to be a more potent natriuretic and diuretic agent than furosemide in direct comparative studies.…”

“…11,12 Atrial natriuretic factor does not enhance the synthesis of prostaglandin E 2 or have the ability to inhibit renal Na ϩ -K ϩ -ATPase. 11,12 The natriuretic property of vessel dilator in CHF subjects is especially impressive in light of the facts that (1) the natriuretic effects of vessel dilator are not blunted in CHF as found in the present investigation and (2) the natriuretic and diuretic effects of vessel dilator are at least equal to atrial natriuretic factor, 1 which has been found to be a more potent natriuretic and diuretic agent than furosemide in direct comparative studies. 21 The natriuresis and diuresis in most of the CHF subjects in the present investigation lasted at least 3 hours, suggesting that vessel dilator may be useful therapeutically for CHF in that its potent diuretic and natriuretic properties are sustained and long lasting.…”

“…All over-the-counter medications were stopped at least 24 hours before the study. Specifically, nonsteroidals, including aspirin, were stopped 24 hours before the study because part of the natriuretic effects of vessel dilator are done by increasing the synthesis of prostaglandin E 2 , which in turn inhibits Na ϩ -K ϩ -ATPase in the kidney, 11,12 and nonsteroidals block this effect in vitro 11,12 and in vivo. 13 (Experimental subject 5, who stopped his ibuprofen 3 days before the study, revealed after the study was completed that he did take a 325-mg aspirin tablet the night before the study.)…”