Renin secretion by fetal lamb kidneys in vitro

Abstract

We studied the content and secretion of renin by renal cortical slices obtained from ovine fetuses at 0.62-0.77 gestation (n = 5 immature) and at 0.84-1.00 gestation (n = 5 mature). Renin content of fresh slices and renin secretion after the incubation of slices in Robinson's medium with or without isoproterenol or dibutyryl (DB) adenosine 3',5'-cyclic monophosphate (cAMP) (10(-4)-10(-8) M) were measured. Renin content of immature fetal kidneys (ng.ml homogenate-1.h-1.mg-1) and basal renin secretion rate [ng (ANG I/h).mg tissue-1.h incubation-1] were 24.3 +/- 3.0 and 1.4 +/- 0.4, respectively. Both of these values were significantly lower (P less than 0.02) than the corresponding results obtained with mature fetal kidneys (67.0 +/- 4.5 and 3.4 +/- 0.5). Renin content and basal secretion rates were strongly correlated (r = 0.78, P less than 0.01). The addition of isoproterenol or DBcAMP induced a significant increase in renin secretion only when incubated with slices from mature fetuses. We conclude that there is a deficit in the beta-adrenoceptor-mediated renin release distal to cAMP formation in immature fetuses, which may be related to low renal content of renin at this stage of development.

Effect of renal denervation on renin gene expression, concentration, and secretion in mature ovine fetus

“…It is of interest that denervation in late gestation resulted in low basal levels of plasma renin and decreased sensitivity to isoproterenol despite normal renal renin concentration. This mimics the pattern of renin secretion seen in early gestation fetuses (24) and may represent withdrawal of some sort of "priming" effect of the renal nerves to sensitize cells destined to secrete renin in late gestation. Exactly how this priming effect would occur is unknown, but Slotkin et al (29) have suggested that early pioneer synapses provide a trophic signal that enables cells to increase their sensitivity to stimulation during the perinatal transition period (30).…”

“…Plasma active renin and prorenin concentrations (ARC and PRC, respectively) were determined by a modification of previously described methods (24). Plasma ARC was measured as a function of the amount of ANG I generated in the presence of excess angiotensinogen (nephrectomized sheep plasma).…”

Inhibition of cyclooxygenase-2: effects on renin secretion and expression in fetal lambs

“…bpm, Beats/min. upregulation of the RAS in the perinatal period may be related to the increase in COX-2 expression observed at this time (32,43).…”

“…Animal studies have found immunoreactive COX-2 to appear first in midgestation (15,41). Furthermore, gestational agedependent responses in renin secretion have been observed in the presence of stimuli such as hemorrhage, hypoxia, furosemide infusion, hypotension, and isoproterenol infusion (9,30,(32)(33)(34)(35). However, chronic stimulation of the RAS can induce renin secretion in immature animals to a pattern resembling that of more mature fetuses (35).…”

“…Activity of the RAS is markedly increased in mammalian species during fetal and neonatal life compared with adults. This is particularly evident during late gestation and appears essential for survival (31,32,43). Mice with mutations of the angiotensinogen gene and those that are homozygous for knockout of the converting enzyme gene demonstrate significant abnormalities in kidney development and rarely survive beyond the infant stage (5,22,23,29).…”