Abstract
Objective
To investigate the effect of renal denervation on renin mRNA levels in fetal and nonpregnant adult ovine renocortical tissue and in isolated juxtaglomerular cells under basal conditions and after stimulation.
Methods
The left kidney was denervated and the right kidney subjected to a sham procedure in nine ovine fetuses (136–41 days’ gestation) and 20 nonpregnant ewes. After 5–7 days the denervated and intact kidneys were obtained, and renin-containing renal cortical cells were isolated and cultured overnight. Then cells were treated with isoproterenol, forskolin, or isomethylbutyl xanthine (IBMX) for 4 hours. Total RNA was isolated and renin mRNA measured by RNase protection assay. Cyclic adenosine monophosphate (cAMP) levels were measured in the incubation medium with a competitive enzyme immunoassay.
Results
In adults, basal renin mRNA levels were significantly lower in denervated than in sham-operated kidneys. No diference was noted between denervated and intact fetal kidneys. Renin mRNA levels were significantly higher in fetal than in adult kidney tissue, and cells from fetuses had greater increases in renin mRNA after stimulation than did cells from adults. Fetal cells also released more cAMP into the incubation medium, and there was a correlation between cAMP and renin mRNA levels.
Conclusions
The data indicate the effects of renal denervation on renin mRNA expression in the kidney are age dependent and that thefetus in late gestation has a mechanism for maintaining renin mRNA levels after denervation, which is absent or nonfunctional in the adult.
Similar content being viewed by others
References
Dzau VJ, Pratt RE. Renin-angiotensin system. In: Fozzad HA, Harber E, Jenning RB, Katz AM, Morgan HE, eds. The heart and cardiovascular system. 2nd ed. New York: Raven Press, 1992:1817–49.
Hackenthal E, Paul M, Ganten D, Taugner R. Morphology, physiology, and molecular biology of renin secretion. Physiol Rev 1990; 70:1067–116.
Kurtz A. Cellular control of renin secretion. Rev Physiol Bio-chem Pharmacol 1989; 113:1–40.
Kurtz A, Wagner C. Cellular control of renin secretion. J Exp Biol 1999; 202:219–25.
Gomez RA. Role of angiotensin in renal vascular development. Kidney Int 1998; 54:S12–6.
Gomez RA, Lynch KR, Sturgill BC, et al. Distribution of renin mRNA and its protein in the developing kidney. Am J Physiol 1989; 257:F850–8.
Gomez RA, Norwood VF. Developmental consequence of the renin-angiotensin system. Am J Kidney Dis 1995; 26:409–31.
Gomez RA, Pupilli C, Everett AD. Molecular and cellular aspects of renin during kidney ontogeny. Pediatr Nephrol 1991; 5: 80–7.
Tufro-McReddie A, Gomez PA. Ontogeny of the renin-angiotensin system. Semin Nephrol 1993; 13:519–30.
Tufro-McReddie A, Johns DW, Geary KM, et al. Angiotensin II type 1 receptor: role in renal growth and gene expression during normal development. Am J Physiol 1994; 266:F911–8.
Carbone GMR, Sheikh AU, Rogers S, Brewer G, Rose JC. Developmental changes in renin gene expression in ovine kidney cortex. Am J Physiol 1993; 264:R591–6.
Rawashdeh NM, Rose JC, Kerr DR. Age-dependent differences in active and inactive renin in the lamb fetus. Biol Neonate 1991; 60:243–8.
Wang J, Perez FM, Rose JC. Developmental changes in renin-containing cells from the ovine fetal kidney. J Soc Gynecol Invest 1997; 4:191–6.
Wang J, Rose JC. Developmental changes in renal renin mRNA half-life and responses to stimulation in fetal lambs. Am J Physiol 1999; 277:R1130–5.
Zhang DY, Lumbers ER, Simonetta G. Changes in renal renin gene expression in fetal sheep. Clin Exp Pharmacol Physiol 1996; 23:682–4.
Mazursky JE, Segar JL, Nuyt AM, Smith BA, Robillard JE. Regulation of renal sympathetic nerve activity at birth. Am J Physiol 1996; 270:R86–93.
Robillard JE, Guillery EN, Segar JL, Merrill DC, Jose PA. Influence of renal nerves on renal function during development. Pediatr Nephrol 1993; 7:667–71.
Segar JL, Hajduczok G, Smith BA, Merrill DC, Robillard JE. Ontogeny of baroreflex control of renal sympathetic nerve activity and heart rate. Am J Physiol 1992; 263:H1819–26.
Rawashdeh NM, Rose JC, Kerr DR. Renin secretion by fetal lamb kidneys in vitro. Am J Physiol 1990; 258:R388–92.
Rawashdeh NM, Rose JC, Ray ND. Differential maturation of β-adrenoceptor-mediated responses in the lamb fetus. Am J Physiol 1988; 255:R794–8.
Draper ML, Wang J, Valego N, Block WA Jr, Rose JC. Effect of renal denervation on renin gene expression, concentration, and secretion in mature ovine fetus. Am J Physiol 2000; 279:R263–70.
Robillard JE, Nakamura KT, Dibona GF. Effects of renal denervation on renal responses to hypoxia in fetal lambs. Am J Physiol 1986; 250:F294–301.
Aldred GP, Fu P, Crawfors RJ, Fernley RT. The sequence and tissue expression of ovine renin. J Mol Endocrinol 1992; 8:3–11.
Chen M, Schnermann J, Smart AM, Brosius FC, Killen PD, Briggs JP. Cyclic AMP selectively increases renin mRNA stability in cultured juxtaglomerular granular cells. J Biol Chem 1993; 268:24138–44.
Holmer S, Rinne B, Eckardt KU, et al. Role of renal nerves for the expression of renin in adult rat kidney. Am J Physiol 1994; 266:F738–45.
Zhang Y, Morgan T, Read G. The role of the renal nerves in renin synthesis. Clin Exp Pharmacol Physiol 1992; 19:827–31.
Wagner C, Hinder M, Kramer BK, Kurtz A. Role of renal nerves in the stimulation of renin system by reduced renal arterial pressure. Hypertension 1999; 34:1101–5.
Page WV, Perlman S, Smith FG, Segar JL, Robillard JE. Renal nerves modulate kidney renin gene expression during the transition from fetal to newborn life. Am J Physiol 1992; 262:R459–63.
Smith FG, Smith BA, Guillery EN, Robillard JE. Role of renal sympathetic nerves in Iambs during the transition from fetal to newborn life. J Clin Invest 1991; 88:1988–94.
El-Dahr SS, Gomez RA, Gray MS, Peach MJ, Carey RM, Chevalier RL. Renal nerves modulate renin gene expression in the developing rat kidney with ureteral obstruction. J Clin Invest 1991; 87:800–10.
Churchill PC. Second messengers in renin secretion. Am J Physiol 1985; 249:F175–84.
Kurtz A. Membrane and secretory properties of renal juxtaglomerular granular cells. Clin Exp Pharmacol Physiol 1997; 24: 536–40.
Kurtz A, Scholz H, Bruna RD. Molecular Mechanisms of renin release. J Cardiovasc Pharmacol 1990; 16(Suppl 4):S1–7.
Gemsa D, Steggemann L, Menzel J, Till G. Release of cyclic AMP from macrophages by stimulation with prostaglandins. J Immunol 1975; 114:1422–4.
Brunton LL, Mayer SE. Extrusion of cyclic AMP from pigeon erythrocytes. J Biol Chem 1979; 254:9714–20.
Lazareno S, Marriott DB, Nahorski R. Differential effects of selective and non-selective neuroleptics on intracellular and extracellular cyclic AMP accumulation in rat striatal slices. Brain Res 1985; 361:91–8.
Slotkin TA, Saleh JL, Zhang J, Seidler FJ. Ontogeny of beta-adrenoceptor/adenylyl cyclase desensitization mechanism: the role of neonatal innervation. Brain Res 1996; 742:317–28.
Author information
Authors and Affiliations
Corresponding author
Additional information
The authors acknowledge Mike Dunlap for technical expertise and Dr. Nancy Valego for continued support.
This work was supported by National Institutes of Health grant HD-17644 and an RJR-Leon Golberg Fellowship.
Rights and permissions
About this article
Cite this article
Ito, H., Wang, J., Strandhoy, J.W. et al. Importance of the Renal Nerves for Basal and Stimulated Renin mRNA Levels in Fetal and Adult Ovine Kidneys. Reprod. Sci. 8, 327–333 (2001). https://doi.org/10.1177/107155760100800604
Published:
Issue Date:
DOI: https://doi.org/10.1177/107155760100800604