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. 1998 Oct 15;102(8):1489–1497. doi: 10.1172/JCI4401

Angiotensin induces the urinary peristaltic machinery during the perinatal period.

Y Miyazaki 1, S Tsuchida 1, H Nishimura 1, J C Pope 4th 1, R C Harris 1, J M McKanna 1, T Inagami 1, B L Hogan 1, A Fogo 1, I Ichikawa 1
PMCID: PMC508998  PMID: 9788961

Abstract

The embryonic development of mammalian kidneys is completed during the perinatal period with a dramatic increase in urine production, as the burden of eliminating nitrogenous metabolic waste shifts from the placenta to the kidney. This urine is normally removed by peristaltic contraction of the renal pelvis, a smooth muscle structure unique to placental mammals. Mutant mice completely lacking angiotensin type 1 receptor genes do not develop a renal pelvis, resulting in the buildup of urine and progressive kidney damage. In mutants the ureteral smooth muscle layer is hypoplastic and lacks peristaltic movements. We show that angiotensin can induce the ureteral smooth muscles in organ cultures of wild-type, but not mutant, ureteral tissues and that, in wild-type mice, expression of both renal angiotensin and the receptor are transiently upregulated at the renal outlet at birth. These results reveal a new role for angiotensin in the unique cellular adaptations of the mammalian kidney to the physiological stresses of postnatal life.

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Selected References

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  1. Avner E. D., Sweeney W. E., Jr, Piesco N. P., Ellis D. Growth factor requirements of organogenesis in serum-free metanephric organ culture. In Vitro Cell Dev Biol. 1985 May;21(5):297–304. doi: 10.1007/BF02620946. [DOI] [PubMed] [Google Scholar]
  2. BOYLAN J. W., COLBOURN E. P., McCANCE R. A. Renal function in the foetal and new-born guinea-pig. J Physiol. 1958 Apr 30;141(2):323–331. doi: 10.1113/jphysiol.1958.sp005976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baker K. M., Aceto J. F. Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells. Am J Physiol. 1990 Aug;259(2 Pt 2):H610–H618. doi: 10.1152/ajpheart.1990.259.2.H610. [DOI] [PubMed] [Google Scholar]
  4. Carpenter C., Honkanen A. A., Mashimo H., Goss K. A., Huang P., Fishman M. C., Asaad M., Dorso C. R., Cheung H. Renal abnormalities in mutant mice. Nature. 1996 Mar 28;380(6572):292–292. doi: 10.1038/380292a0. [DOI] [PubMed] [Google Scholar]
  5. Chen X., Li W., Yoshida H., Tsuchida S., Nishimura H., Takemoto F., Okubo S., Fogo A., Matsusaka T., Ichikawa I. Targeting deletion of angiotensin type 1B receptor gene in the mouse. Am J Physiol. 1997 Mar;272(3 Pt 2):F299–F304. doi: 10.1152/ajprenal.1997.272.3.F299. [DOI] [PubMed] [Google Scholar]
  6. Cheng E. Y., Maizels M., Chou P., Hartanto V., Shapiro E. Response of the newborn ureteropelvic junction complex to induced and later reversed partial ureteral obstruction in the rabbit model. J Urol. 1993 Aug;150(2 Pt 2):782–789. doi: 10.1016/s0022-5347(17)35613-6. [DOI] [PubMed] [Google Scholar]
  7. Ciuffo G. M., Viswanathan M., Seltzer A. M., Tsutsumi K., Saavedra J. M. Glomerular angiotensin II receptor subtypes during development of rat kidney. Am J Physiol. 1993 Aug;265(2 Pt 2):F264–F271. doi: 10.1152/ajprenal.1993.265.2.F264. [DOI] [PubMed] [Google Scholar]
  8. Constantinou C. E., Hrynczuk J. R. Urodynamics of the upper urinary tract. Invest Urol. 1976 Nov;14(3):233–240. [PubMed] [Google Scholar]
  9. Constantinou C. E. Renal pelvic pacemaker control of ureteral peristaltic rate. Am J Physiol. 1974 Jun;226(6):1413–1419. doi: 10.1152/ajplegacy.1974.226.6.1413. [DOI] [PubMed] [Google Scholar]
  10. De Silva P. E., Husain A., Smeby R. R., Khairallah P. A. Measurement of immunoreactive angiotensin peptides in rat tissues: some pitfalls in angiotensin II analysis. Anal Biochem. 1988 Oct;174(1):80–87. doi: 10.1016/0003-2697(88)90521-0. [DOI] [PubMed] [Google Scholar]
  11. Esther C. R., Jr, Howard T. E., Marino E. M., Goddard J. M., Capecchi M. R., Bernstein K. E. Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab Invest. 1996 May;74(5):953–965. [PubMed] [Google Scholar]
  12. Friberg P., Sundelin B., Bohman S. O., Bobik A., Nilsson H., Wickman A., Gustafsson H., Petersen J., Adams M. A. Renin-angiotensin system in neonatal rats: induction of a renal abnormality in response to ACE inhibition or angiotensin II antagonism. Kidney Int. 1994 Feb;45(2):485–492. doi: 10.1038/ki.1994.63. [DOI] [PubMed] [Google Scholar]
  13. Gasc J. M., Shanmugam S., Sibony M., Corvol P. Tissue-specific expression of type 1 angiotensin II receptor subtypes. An in situ hybridization study. Hypertension. 1994 Nov;24(5):531–537. doi: 10.1161/01.hyp.24.5.531. [DOI] [PubMed] [Google Scholar]
  14. Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gibbons G. H., Pratt R. E., Dzau V. J. Vascular smooth muscle cell hypertrophy vs. hyperplasia. Autocrine transforming growth factor-beta 1 expression determines growth response to angiotensin II. J Clin Invest. 1992 Aug;90(2):456–461. doi: 10.1172/JCI115881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Itatani H., Koide T., Okuyama A., Mizutani S., Sonoda T. Development of the calyceal system in the human fetus. Invest Urol. 1979 Mar;16(5):388–394. [PubMed] [Google Scholar]
  17. Ito M., Oliverio M. I., Mannon P. J., Best C. F., Maeda N., Smithies O., Coffman T. M. Regulation of blood pressure by the type 1A angiotensin II receptor gene. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3521–3525. doi: 10.1073/pnas.92.8.3521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jose P. A., Slotkoff L. M., Montgomery S., Calcagno P. L., Eisner G. Autoregulation of renal blood flow in the puppy. Am J Physiol. 1975 Oct;229(4):983–988. doi: 10.1152/ajplegacy.1975.229.4.983. [DOI] [PubMed] [Google Scholar]
  19. Kotchen T. A., Strickland A. L., Rice T. W., Walters D. R. A study of the renin-angiotensin system in newborn infants. J Pediatr. 1972 Jun;80(6):938–946. doi: 10.1016/s0022-3476(72)80005-2. [DOI] [PubMed] [Google Scholar]
  20. Krege J. H., John S. W., Langenbach L. L., Hodgin J. B., Hagaman J. R., Bachman E. S., Jennette J. C., O'Brien D. A., Smithies O. Male-female differences in fertility and blood pressure in ACE-deficient mice. Nature. 1995 May 11;375(6527):146–148. doi: 10.1038/375146a0. [DOI] [PubMed] [Google Scholar]
  21. Matsusaka T., Nishimura H., Utsunomiya H., Kakuchi J., Niimura F., Inagami T., Fogo A., Ichikawa I. Chimeric mice carrying 'regional' targeted deletion of the angiotensin type 1A receptor gene. Evidence against the role for local angiotensin in the in vivo feedback regulation of renin synthesis in juxtaglomerular cells. J Clin Invest. 1996 Oct 15;98(8):1867–1877. doi: 10.1172/JCI118988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nagata M., Tanimoto K., Fukamizu A., Kon Y., Sugiyama F., Yagami K., Murakami K., Watanabe T. Nephrogenesis and renovascular development in angiotensinogen-deficient mice. Lab Invest. 1996 Nov;75(5):745–753. [PubMed] [Google Scholar]
  23. Nightingale S. L. From the Food and Drug Administration. JAMA. 1992 May 13;267(18):2445–2445. doi: 10.1001/jama.267.18.2445. [DOI] [PubMed] [Google Scholar]
  24. Niimura F., Labosky P. A., Kakuchi J., Okubo S., Yoshida H., Oikawa T., Ichiki T., Naftilan A. J., Fogo A., Inagami T. Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest. 1995 Dec;96(6):2947–2954. doi: 10.1172/JCI118366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Peters C. A., Carr M. C., Lais A., Retik A. B., Mandell J. The response of the fetal kidney to obstruction. J Urol. 1992 Aug;148(2 Pt 2):503–509. doi: 10.1016/s0022-5347(17)36640-5. [DOI] [PubMed] [Google Scholar]
  26. Pryde P. G., Sedman A. B., Nugent C. E., Barr M., Jr Angiotensin-converting enzyme inhibitor fetopathy. J Am Soc Nephrol. 1993 Mar;3(9):1575–1582. doi: 10.1681/ASN.V391575. [DOI] [PubMed] [Google Scholar]
  27. Rabinowitz R., Peters M. T., Vyas S., Campbell S., Nicolaides K. H. Measurement of fetal urine production in normal pregnancy by real-time ultrasonography. Am J Obstet Gynecol. 1989 Nov;161(5):1264–1266. doi: 10.1016/0002-9378(89)90679-0. [DOI] [PubMed] [Google Scholar]
  28. Sadoshima J., Izumo S. Molecular characterization of angiotensin II--induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res. 1993 Sep;73(3):413–423. doi: 10.1161/01.res.73.3.413. [DOI] [PubMed] [Google Scholar]
  29. Sedman A. B., Kershaw D. B., Bunchman T. E. Recognition and management of angiotensin converting enzyme inhibitor fetopathy. Pediatr Nephrol. 1995 Jun;9(3):382–385. doi: 10.1007/BF02254221. [DOI] [PubMed] [Google Scholar]
  30. Starr N. T., Maizels M., Chou P., Brannigan R., Shapiro E. Microanatomy and morphometry of the hydronephrotic "obstructed" renal pelvis in asymptomatic infants. J Urol. 1992 Aug;148(2 Pt 2):519–524. doi: 10.1016/s0022-5347(17)36643-0. [DOI] [PubMed] [Google Scholar]
  31. Sugaya T., Nishimatsu S., Tanimoto K., Takimoto E., Yamagishi T., Imamura K., Goto S., Imaizumi K., Hisada Y., Otsuka A. Angiotensin II type 1a receptor-deficient mice with hypotension and hyperreninemia. J Biol Chem. 1995 Aug 11;270(32):18719–18722. doi: 10.1074/jbc.270.32.18719. [DOI] [PubMed] [Google Scholar]
  32. Taylor G. M., Peart W. S., Porter K. A., Zondek L. H., Zondek T. Concentration and molecular forms of active and inactive renin in human fetal kidney, amniotic fluid and adrenal gland: evidence for renin-angiotensin system hyperactivity in 2nd trimester of pregnancy. J Hypertens. 1986 Feb;4(1):121–129. doi: 10.1097/00004872-198602000-00019. [DOI] [PubMed] [Google Scholar]
  33. Tsuchida S., Matsusaka T., Chen X., Okubo S., Niimura F., Nishimura H., Fogo A., Utsunomiya H., Inagami T., Ichikawa I. Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes. J Clin Invest. 1998 Feb 15;101(4):755–760. doi: 10.1172/JCI1899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Turla M. B., Thompson M. M., Corjay M. H., Owens G. K. Mechanisms of angiotensin II- and arginine vasopressin-induced increases in protein synthesis and content in cultured rat aortic smooth muscle cells. Evidence for selective increases in smooth muscle isoactin expression. Circ Res. 1991 Jan;68(1):288–299. doi: 10.1161/01.res.68.1.288. [DOI] [PubMed] [Google Scholar]
  35. Yoshida H., Kakuchi J., Guo D. F., Furuta H., Iwai N., van der Meer-de Jong R., Inagami T., Ichikawa I. Analysis of the evolution of angiotensin II type 1 receptor gene in mammals (mouse, rat, bovine and human). Biochem Biophys Res Commun. 1992 Jul 31;186(2):1042–1049. doi: 10.1016/0006-291x(92)90852-c. [DOI] [PubMed] [Google Scholar]
  36. Yoshida Y., Fogo A., Ichikawa I. Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis. Kidney Int. 1989 Feb;35(2):654–660. doi: 10.1038/ki.1989.35. [DOI] [PubMed] [Google Scholar]

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