Studies on the Immaturity of the ADH-Dependent cAMP System in Conscious Newborn Piglets—Possible Impairing Effects of Renal Prostaglandins

Abstract

SummaryIn 24 conscious newborn piglets the effects of 20 &kg body weight IV 1-deamino-&~-arginine-vasopressin (DDAVP) in group 1, 5 mg/kg P O indomethacin in group 2, and the combined effects of both drugs in group 3 were studied by measuring urinary flow rate. urinary osmolality, creatinine clearance, total urinary and nephrogenols cyclic-adknosine 3':s'-monophosphate (CAMP) excretion. medullary cAMP content. and renal prostaglandin (PG)E2 and PGF2,, excreiion. DDAVP alone had no-signifilcant effects on the above parameters, whereas indomethacin alone reduced only the PG excretion significantly. When both drugs were administered simultaneously, urinary concentration increased significantly Recent in vivo studies provided evidence that the restricted urinary concentrating capacity of the neonatal kidney results from the inability of the medullary cyclic adenosine 3':5'-monophosphate (CAMP) system to accumulate cAMP sufficiently in the presence of antidiuretic hormone (ADH) (14) in addition to the reduced glomerular filtration rate (2). the structural immaturity of the loop of Henle (5), and the low excretion rate of urea (7). Some observations indicate that the unresponsiveness of the cAMP system to ADH may result not only from a functional immaturity of the medullary adenylate cyclase (20,22), but additionally from the interference of renal prostaglandins (PGs) of the E-series with the hydro-osmotic action of ADH. This view is based on the following observations: (1) in isolated collecting ducts, the effect of ADH on the water permeability was blunted when PGEl was applied (10); (2) conversely, in adult mammals when PG synthesis was inhibited the effect of ADH on water reabsorption was increased (1, 3. 8. 17).High concentrations of PGs were found in urine of fetal lambs (23). and high PGEl levels were inversely correlated with urinary cAMP excretion in premature infants (15). If a relatively high PGE? formation in the kidney of neonates is indeed a restrictive parameter for renal medullary cAMP accumulation, it should be possible to increase the effect of ADH on urinary concentration by inhibiting PG synthesis.Therefore. we measured urinary concentration in newborn piglets, both before and after the administration of either DDAVP or indomethacin alone and after administration of DDAVP plus indomethacin. The studies were performed in conscious animals because it has been shown that in the unanaesthetized animal indomethacin does not change renal blood flow (24), whereas administration of this drug in the anaesthetized dog is associated with a marked fall in renal blood flow (16). MATERIALS A N D METHODS EXPERIMENTALStudies were carried out on 24 male conscious piglets (strain. Deutsche Landrasse) within the first 24 hr after birth. The animals weighed between 1000 and 1700 g and had free access to suck. The following protocol was used.Control Period. In all animals used. first all urine in the bladder was removed by puncturing the bladder suprapubically. Then the urethra was closed by glue and plaster, and each ...

Renal Response to Vasopressin in Premature Infants: What Is New?

“…In support of this con cept Joppich et al [ 11 ] observed that in new born piglets DDAVP administration alone had no significant effect on urinary cAMP excretion and urine osmolality whereas DDAVP given with indomethacin resulted in a significant increase in medullary cAMP content, urinary cAMP excretion and urine osmolality.…”

Water transport in the immature rabbit collecting duct

“…A progressive decline in urinary concentration of PGE 2 during ontogenesis is accompanied by an increase in urine osmolality [13]. Moreover, studies on newborn piglets have shown that administration of indomethacin leads to increased urine osmolality and urinary cAMP levels [14], suggesting that prostaglandins mediate the hyposthenuria of the immature kidney. In contrast, our results showed that despite inhibition of endogenous prostaglandin production by indomethacin, the AVP-stimulated water permeability in the iCCD remained significantly decreased.…”

“…Elevated levels of prostaglandins have been found in urine from fetal lambs and preterm human infants [8,13]. Furthermore, inhibition of endogenous prostaglandin synthesis by indomethacin increases urinary osmolality and nephrogenous cAMP excretion in newborn piglets, suggesting that the renal resistane to AVP could be mediated by prostaglandins [14].…”

Urinary Arginine Vasopressin: Pattern of Excretion in the Neonatal Period

“…prostaglandin E? (35). Such an antagonist might explain the uncommon occurrence of the syndrome of inappropriate antidiuretic hormone in sick neonates despite high levels of AVP secretion.…”