Role of prostaglandins in mediating the renal effects of atrial natriuretic factor.

Abstract

SUMMARY Tbe natriuretk response to the intrarenal administration of atrial natriuretic factor (ANF)is accompanied by an increase in tbe synthesis of prostaglandins and by a redistribution of renal blood flow from the superficial to the deep cortex. This study was undertaken to define whether prostaglandins mediate the ANF-induced redistribution of renal blood flow and if prostaglandins and renal blood flow redistribution contribute to the natriuretic actions of ANF. In anesthetized dogs, the Intrarenal administration of indomethadn (10 jtg/kg/min) or the intravenous administration of meclofenamate (5 mg/kg) completely prevented the sixfold and twofold increments in urinary prostaglandin E 2 and 6-keto-prostaglandin F l a excretion, respectively; it also abolished the redistribution of renal blood flow to the deep cortex. However, ANF induced a similar natriuresis before (from 53 ± 17 to 281 ± 48 /tEq/min) and after (from 45 ± 13 to 273 ± 60 /iEq/min) the administration of prostaglandin synthesis inhibitors. It is concluded that the ANF-induced redistribution of renal blood flow to the deep cortex is prostaglandinmediated but that neither redistribution nor increased prostaglandin synthesis Is an important mediator of ANF's natriuretic action. (Hypertension 12: 274-278, 1988) KEY WORDS • atrial natriuretic factor • intrarenal blood flow distribution • prostaglandin synthesis inhibitors • sodium excretionW E have recently found that the natriuretic response to the intrarenal infusion of atrial natriuretic factor (ANF) at doses that do not alter mean arterial pressure (MAP), renal blood flow (RBF), or glomerular filtration rate (GFR) is accompanied by a significant increase in urinary excretion of prostaglandins and by a redistribution of RBF from the superficial to the juxtamedullary cortex.1 Previous studies have shown that enhanced prostaglandin synthesis or selective prostaglandin infusion increases juxtamedullary cortical flow.2 -5 Others have shown that blockade of prostaglandin synthesis decreases juxtamedullary cortical flow more than superficial cortical flow. 5 -7 Increases in medullary flow have been shown to produce natriuresis, 8 -9 as has increased prostaglan-

Atrial natriuretic peptide and urinary prostaglandins in man.

“…Since no correlations could be found between the urinary excretion of any PG and the natriuresis, it appears unlikely that renal PGs are involved in the natriuretic effect of ANP. This finding confirms the results obtained in humans (Miyamori et al, 1987) and animals (Keeler, 1982;Salazar et al, 1988) demonstrating that pharmacological blockade of PG biosynthesis by cyclo-oxygenase inhibition fails to attenuate the natriuresis elicited by ANP infusion. In contrast to natriuresis, the ANP-induced diuresis might rely partly upon the stimulation of renal PG biosynthesis.…”

“…Since infusion of PGE2 (Tannenbaum et al, 1975) and PGI2 (Gullner et al, 1980), results in an increased sodium and water excretion, it was suggested that PGs could be involved in the renal effects of ANP. However, the failure of cyclo-oxygenase inhibitors to decrease the ANP-induced natriuresis (Keeler, 1982;Salazar et al, 1988) argues against such a mechanism and strongly suggests that, in animals, renal PGs are presumably not involved in the effects of ANP. In man, such a conclusion needs to be confirmed since the evolution of renal PGs following ANP administration has not been yet described in healthy subjects and moreover the reported results differ from those obtained in animals.…”

Prostaglandins regulate the synthesis and secretion of the atrial natriuretic peptide.

“…They are important regulators of cardiovascular and renal physiology with potent effects on platelet function, vascular reactivity, renal blood flow, and the handling of salt and water in the kidney (13). PGs have largely been excluded as playing an important role in mediating ANP bioactivity (14)(15)(16), but their role in regulating ANP release has been studied only to a limited degree (17).…”

Water Immersion Increases Urinary Excretion of Aquaporin-2 in Healthy Humans

“…Therefore, the observation that HOWI induces a significant increase in the natriuretic atrial plasma factor and urinary excretion of AQP2 in the absence of an increase in the plasma values of AVP, suggests that ANF may be a trigger for AQP2 expression, as already in part demonstrated by Patil et al [26]with AQP1 on Xenopus oocytes or the effect may be indirect, through the renal biosynthesis of prostaglandins (PGs) [27, 28]. In fact it has been observed in experimental conditions that immersion is followed by an increase in PG secretion, which reflects increased renal PG synthesis [29].…”