Skip to main content Accessibility help
×
Home
Hostname: page-component-6f6fcd54b-n4hhg Total loading time: 0.34 Render date: 2021-05-11T14:17:42.750Z Has data issue: true Feature Flags: {}

The effect of hypoxia-induced intrauterine growth restriction on renal artery function

Published online by Cambridge University Press:  25 April 2012

M. T. C. Verschuren
Affiliation:
Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
J. S. Morton
Affiliation:
Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, Canada
A. Abdalvand
Affiliation:
Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, Canada
Y. Mansour
Affiliation:
Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, Canada
C. F. Rueda-Clausen
Affiliation:
Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, Canada Department of Physiology, University of Alberta, Edmonton, Canada
C. A. Compston
Affiliation:
Renal Division, Department of Medicine, University of Alberta, Edmonton, Alberta
V. Luyckx
Affiliation:
Renal Division, Department of Medicine, University of Alberta, Edmonton, Alberta
S. T. Davidge
Affiliation:
Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, Canada Department of Physiology, University of Alberta, Edmonton, Canada
Corresponding

Abstract

The risk of developing cardiovascular diseases is known to begin before birth and the impact of the intrauterine environment on subsequent adult health is currently being investigated from many quarters. Following our studies demonstrating the impact of hypoxia in utero and consequent intrauterine growth restriction (IUGR) on the rat cardiovascular system, we hypothesized that changes extend throughout the vasculature and alter function of the renal artery. In addition, we hypothesized that hypoxia induces renal senescence as a potential mediator of altered vascular function. We demonstrated that IUGR females had decreased responses to the adrenergic agonist phenylephrine (PE; pEC50 6.50 ± 0.05 control v. 6.17 ± 0.09 IUGR, P < 0.05) and the endothelium-dependent vasodilator methylcholine (MCh; E max 89.8 ± 7.0% control v. 41.0 ± 6.5% IUGR, P < 0.001). In IUGR females, this was characterised by increased basal nitric oxide (NO) modulation of vasoconstriction (PE pEC50 6.17 ± 0.09 IUGR v. 6.42 ± 0.08 in the presence of the NO synthase inhibitor N-nitro-l-arginine methyl ester hydrochloride (l-NAME; P < 0.01) but decreased activated NO modulation (no change in MCh responses in the presence of l-NAME), respectively. In contrast, IUGR males had no changes in PE or MCh responses but demonstrated increased basal NO (PE pEC50 6.29 ± 0.06 IUGR v. 6.42 ± 0.12 plus l-NAME, P < 0.01) and activated NO (E max 37.8 ± 9.4% control v. −0.8 ± 13.0% plus l-NAME, P < 0.05) modulation. No significant changes were found in gross kidney morphology, proteinuria or markers of cellular senescence in either sex. In summary, renal vascular function was altered by hypoxia in utero in a sex-dependent manner but was unlikely to be mediated by premature renal senescence.

Type
Original Article
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

Access options

Get access to the full version of this content by using one of the access options below.

Footnotes

a

These authors have contributed equally to the preparation of this manuscript.

References

1. Barker, DJP. Adult consequences of fetal growth restriction. Clin Obstet Gynecol. 2006; 49, 270283.CrossRefGoogle ScholarPubMed
2. Barker, DJ. In utero programming of chronic disease. Clin Sci (Lond). 1998; 95, 115128.CrossRefGoogle ScholarPubMed
3. Barker, DJ. In utero programming of cardiovascular disease. Theriogenology. 2000; 53, 555574.CrossRefGoogle ScholarPubMed
4. Barker, DJ. Fetal programming of coronary heart disease. Trends Endocrinol Metab: TEM. 2002; 13, 364368.CrossRefGoogle ScholarPubMed
5. Goodfellow, J, Bellamy, MF, Gorman, ST, et al. . Endothelial function is impaired in fit young adults of low birth weight. Cardiovasc Res. 1998; 40, 600606.CrossRefGoogle ScholarPubMed
6. Halvorsen, CP, Andolf, E, Hu, J, et al. . Discordant twin growth in utero and differences in blood pressure and endothelial function at 8 years of age. J Inter Med. 2006; 259, 155163.CrossRefGoogle ScholarPubMed
7. Leeson, CPM, Kattenhorn, M, Morley, R, Lucas, A, Deanfield, JE. Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life. Circulation. 2001; 103, 12641268.CrossRefGoogle ScholarPubMed
8. Leeson, CPM, Whincup, PH, Cook, DG, et al. . Flow-mediated dilation in 9- to 11-year-old children: the influence of intrauterine and childhood factors. Circulation. 1997; 96, 22332238.CrossRefGoogle ScholarPubMed
9. Stein, AD, Zybert, PA, van der Pal-de Bruin, K, Lumey, L. Exposure to famine during gestation, size at birth, and blood pressure at age 59 y: evidence from the dutch famine. Eur J Epidemiol. 2006; 21, 759765.CrossRefGoogle Scholar
10. Kajantie, E, Barker, DJP, Osmond, C, Forsen, T, Eriksson, JG. Growth before 2 years of age and serum lipids 60 years later: the Helsinki Birth Cohort Study. Int J Epidemiol. 2008; 37, 280289.CrossRefGoogle ScholarPubMed
11. Fall, CHD, Sachdev, HS, Osmond, C, et al. Adult metabolic syndrome and impaired glucose tolerance are associated with different patterns of body mass index gain during infancy: data from the New Delhi Birth Cohort. Diabetes Care. 2008; 31, 23492356.Google Scholar
12. Alastalo, H, Raikkonen, K, Pesonen, A-K, et al. . Cardiovascular health of Finnish war evacuees 60 years later. Ann Med. 2009; 41, 6672.CrossRefGoogle ScholarPubMed
13. Jobgen, WS, Ford, SP, Jobgen, SC, et al. . Baggs ewes adapt to maternal undernutrition and maintain conceptus growth by maintaining fetal plasma concentrations of amino acids. J Anim Sci. 2008; 86, 820826.CrossRefGoogle ScholarPubMed
14. Morton, JS, Rueda-Clausen, CF, Davidge, ST. Mechanisms of endothelium-dependent vasodilation in male and female, young and aged offspring born growth restricted. Am J Physiol Regul Integr Comp Physiol. 2010; 298, R930R938.CrossRefGoogle Scholar
15. Hemmings, DG, Williams, SJ, Davidge, ST. Increased myogenic tone in 7-month-old adult male but not female offspring from rat dams exposed to hypoxia during pregnancy. Am J Physiol Heart Circ Physiol. 2005; 289, H674H682.CrossRefGoogle Scholar
16. Williams, SJ, Hemmings, DG, Mitchell, JM, McMillen, IC, Davidge, ST. Effects of maternal hypoxia or nutrient restriction during pregnancy on endothelial function in adult male rat offspring. J Physiol. 2005; 565, 125135.CrossRefGoogle ScholarPubMed
17. Luyckx, VA, Brenner, BM. The clinical importance of nephron mass. J Am Soc Nephrol. 2010; 21, 898910.CrossRefGoogle ScholarPubMed
18. Latini, G, De Mitri, B, Del Vecchio, A, et al. . Foetal growth of kidneys, liver and spleen in intrauterine growth restriction: “programming” causing “metabolic syndrome” in adult age. Acta Paediatr. 2004; 93, 16351639.CrossRefGoogle Scholar
19. Manalich, R, Reyes, L, Herrera, M, Melendi, C, Fundora, I. Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int. 2000; 58, 770773.CrossRefGoogle ScholarPubMed
20. Marchand, MC, Langley-Evans, SC. Intrauterine programming of nephron number: the fetal flaw revisited. J Nephrol. 2001; 14, 327331.Google ScholarPubMed
21. Schreuder, MF, Nyengaard, JR, Fodor, M, van Wijk, JA, Delemarre-van de Waal, HA. Glomerular number and function are influenced by spontaneous and induced low birth weight in rats. J Am Soc Nephrol. 2005; 16, 29132919.CrossRefGoogle ScholarPubMed
22. Sanders, MW, Fazzi, GE, Janssen, GM, et al. . Reduced uteroplacental blood flow alters renal arterial reactivity and glomerular properties in the rat offspring. Hypertension. 2004; 43, 12831289.CrossRefGoogle ScholarPubMed
23. Hughson, M, Farris, AB III, Douglas-Denton, R, Hoy, WE, Bertram, JF. Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int. 2003; 63, 21132122.CrossRefGoogle ScholarPubMed
24. Brenner, BM, Garcia, DL, Anderson, S. Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens. 1988; 1(Pt 1), 335347.CrossRefGoogle ScholarPubMed
25. Keller, G, Zimmer, G, Mall, G, Ritz, E, Amann, K. Nephron number in patients with primary hypertension. N Engl J Med. 2003; 348, 101108.CrossRefGoogle ScholarPubMed
26. Vehaskari, VM, Aviles, DH, Manning, J. Prenatal programming of adult hypertension in the rat. Kidney Int. 2001; 59, 238245.CrossRefGoogle ScholarPubMed
27. Celsi, G, Kistner, A, Aizman, R, et al. . Prenatal dexamethasone causes oligonephronia, sodium retention, and higher blood pressure in the offspring. Pediatr Res. 1998; 44, 317322.CrossRefGoogle ScholarPubMed
28. Dagan, A, Habib, S, Gattineni, J, Dwarakanath, V, Baum, M. Prenatal programming of rat thick ascending limb chloride transport by low-protein diet and dexamethasone. Am J Physiol Regul Integr Comp Physiol. 2009; 297, R93RR9.CrossRefGoogle ScholarPubMed
29. Nehiri, T, Duong Van Huyen, J-P, Viltard, M, et al. . Exposure to maternal diabetes induces salt-sensitive hypertension and impairs renal function in adult rat offspring. Diabetes. 2008; 57, 21672175.CrossRefGoogle ScholarPubMed
30. Franco, MdCP, Nigro, D, Fortes, ZB, et al. . Intrauterine undernutrition – renal and vascular origin of hypertension. Cardiovasc Res. 2003; 60, 228234.CrossRefGoogle Scholar
31. Manning, J, Beutler, K, Knepper, MA, Vehaskari, VM. Upregulation of renal BSC1 and TSC in prenatally programmed hypertension. Am J Physiol Renal Physiol. 2002; 283, F202F206.CrossRefGoogle ScholarPubMed
32. Bogdarina, I, Welham, S, King, PJ, Burns, SP, Clark, AJL. Epigenetic modification of the renin–angiotensin system in the fetal programming of hypertension. Circ Res. 2007; 100, 520526.CrossRefGoogle ScholarPubMed
33. Nwagwu, MO, Cook, A, Langley-Evans, SC. Evidence of progressive deterioration of renal function in rats exposed to a maternal low-protein diet in utero. Br J Nutr. 2000; 83, 7985.Google ScholarPubMed
34. Sahajpal, V, Ashton, N. Renal function and angiotensin AT1 receptor expression in young rats following intrauterine exposure to a maternal low-protein diet. Clin Sci. 2003; 104, 607614.CrossRefGoogle ScholarPubMed
35. Franco, MCP, Casarini, DE, Carneiro-ramos, MS, et al. . Circulating renin–angiotensin system and catecholamines in childhood: is there a role for birthweight? Clin Sci. 2008; 114, 375380.CrossRefGoogle Scholar
36. Bertram, C, Trowern, AR, Copin, N, Jackson, AA, Whorwood, CB. The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11{beta}-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology. 2001; 142, 28412853.CrossRefGoogle ScholarPubMed
37. Struwe, E, Berzl, GM, Schild, RL, et al. . Simultaneously reduced gene expression of cortisol-activating and cortisol-inactivating enzymes in placentas of small-for-gestational-age neonates. Am J Obstet Gynecol. 2007; 197, 43.e143.e6.CrossRefGoogle ScholarPubMed
38. Plank, C, Nüsken, KD, Menendez-Castro, C, et al. . Intrauterine growth restriction following ligation of the uterine arteries leads to more severe glomerulosclerosis after mesangioproliferative glomerulonephritis in the offspring. Am J Nephrol. 2010; 32, 287295.CrossRefGoogle ScholarPubMed
39. Moritz, KM, Dodic, M, Wintour, EM. Kidney development and the fetal programming of adult disease. Bioessays. 2003; 25, 212220.CrossRefGoogle ScholarPubMed
40. Tarry-Adkins, JL, Martin-Gronert, MS, Chen, J-H, Cripps, RL, Ozanne, SE. Maternal diet influences DNA damage, aortic telomere length, oxidative stress, and antioxidant defense capacity in rats. FASEB J. 2008; 22, 20372044.CrossRefGoogle ScholarPubMed
41. Luyckx, VA, Compston, CA, Simmen, T, Mueller, TF. Accelerated senescence in kidneys of low-birth-weight rats after catch-up growth. Am J Physiol Renal Physiol. 2009; 297, F1697F1705.CrossRefGoogle ScholarPubMed
42. Alexander, BT, Hendon, AE, Ferril, G, Dwyer, TM. Renal denervation abolishes hypertension in low-birth-weight offspring from pregnant rats with reduced uterine perfusion. Hypertension. 2005; 45, 754758.CrossRefGoogle ScholarPubMed
43. Ojeda, NB, Johnson, WR, Dwyer, TM, Alexander, BT. Early renal denervation prevents development of hypertension in growth-restricted offspring. Clin Exp Pharmacol Physiol. 2007; 34, 12121216.CrossRefGoogle ScholarPubMed
44. Shaul, PW, Cha, CJ, Oh, W. Neonatal sympathoadrenal response to acute hypoxia: impairment after experimental intrauterine growth retardation. Pediatr Res. 1989; 25, 466472.CrossRefGoogle ScholarPubMed
45. Jansson, T, Lambert, GW. Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous system activity in the rat at 3–4 months of age. J Hypertens. 1999; 17, 12391248.CrossRefGoogle ScholarPubMed
46. Sanders, M, Fazzi, G, Janssen, G, Blanco, C, De Mey, J. Prenatal stress changes rat arterial adrenergic reactivity in a regionally selective manner. Eur J Pharmacol. 2004; 488, 147155.CrossRefGoogle Scholar
47. Mazzuca, MQ, Wlodek, ME, Dragomir, NM, Parkington, HC, Tare, M. Uteroplacental insufficiency programs regional vascular dysfunction and alters arterial stiffness in female offspring. J Physiol. 2010; 588, 19972010.CrossRefGoogle ScholarPubMed
48. Sanders, MW, Fazzi, GE, Janssen, GMJ, et al. . Reduced uteroplacental blood flow alters renal arterial reactivity and glomerular properties in the rat offspring. Hypertension. 2004; 43, 12831289.CrossRefGoogle ScholarPubMed
49. Rueda-Clausen, CF, Morton, JS, Davidge, ST. Effects of hypoxia-induced intrauterine growth restriction on cardiopulmonary structure and function during adulthood. Cardiovasc Res. 2009; 81, 713722.CrossRefGoogle ScholarPubMed
50. Williams, SJ, Campbell, ME, McMillen, IC, Davidge, ST. Differential effects of maternal hypoxia or nutrient restriction on carotid and femoral vascular function in neonatal rats. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R360R367.CrossRefGoogle ScholarPubMed
51. Xu, Y, Williams, SJ, O'Brien, D, Davidge, ST. Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs postischemic recovery in adult male offspring. FASEB J. 2006; 20, 12511253.CrossRefGoogle ScholarPubMed
52. Morton, JS, Rueda-Clausen, CF, Davidge, ST. Flow-mediated vasodilation is impaired in adult rat offspring exposed to prenatal hypoxia. J Appl Physiol. 2011; 110, 10731082.CrossRefGoogle ScholarPubMed
53. Rueda-Clausen, CF, Morton, JS, Lopaschuk, GD, Davidge, ST. Long-term effects of intrauterine growth restriction on cardiac metabolism and susceptibility to ischaemia/reperfusion. Cardiovasc Res. 2011; 90, 285294.CrossRefGoogle ScholarPubMed
54. Kagota, S, Yamaguchi, Y, Nakamura, K, Kunitomo, M. Altered endothelium-dependent responsiveness in the aortas and renal arteries of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus. Gen Pharmacol. 2000; 34, 201209.CrossRefGoogle ScholarPubMed
55. Bussemaker, E, Popp, R, Fisslthaler, B, et al. . Aged spontaneously hypertensive rats exhibit a selective loss of EDHF-mediated relaxation in the renal artery. Hypertension. 2003; 42, 562568.CrossRefGoogle ScholarPubMed
56. Michel, FS, Man, GS, Man, RY, Vanhoutte, PM. Hypertension and the absence of EDHF-mediated responses favour endothelium-dependent contractions in renal arteries of the rat. Br J Pharmacol. 2008; 155, 217226.CrossRefGoogle ScholarPubMed
57. Orescanin, Z, Milovanovic, SR. Effect of l-arginine on the relaxation caused by sodium nitroprusside on isolated rat renal artery. Acta physiologica Hungarica. 2006; 93, 271283.CrossRefGoogle ScholarPubMed
58. Kagota, S, Tamashiro, A, Yamaguchi, Y, Nakamura, K, Kunitomo, M. Excessive salt or cholesterol intake alters the balance among endothelium-derived factors released from renal arteries in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1999; 34, 533539.CrossRefGoogle ScholarPubMed
59. Jiang, F, Li, CG, Rand, MJ. Mechanisms of nitric oxide-independent relaxations induced by carbachol and acetylcholine in rat isolated renal arteries. Br J Pharmacol. 2000; 130, 11911200.CrossRefGoogle ScholarPubMed
60. Franco, MdCP, Arruda, RMMP, Dantas, APV, et al. . Intrauterine undernutrition: expression and activity of the endothelial nitric oxide synthase in male and female adult offspring. Cardiovasc Res. 2002; 56, 145153.CrossRefGoogle Scholar

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

The effect of hypoxia-induced intrauterine growth restriction on renal artery function
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

The effect of hypoxia-induced intrauterine growth restriction on renal artery function
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

The effect of hypoxia-induced intrauterine growth restriction on renal artery function
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *