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The effect of late gestation foetal hypoglycaemia on cardiovascular and endocrine function in sheep

Published online by Cambridge University Press:  10 December 2009

J. K. Cleal*
Affiliation:
The Institute of Developmental Sciences, Southampton General Hospital, University of Southampton, Hampshire, UK
S. Bagby
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA
M. A. Hanson
Affiliation:
The Institute of Developmental Sciences, Southampton General Hospital, University of Southampton, Hampshire, UK
H. M. Gardiner
Affiliation:
Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College, Queen Charlotte’s and Chelsea Hospital, London, UK
L. R. Green
Affiliation:
The Institute of Developmental Sciences, Southampton General Hospital, University of Southampton, Hampshire, UK
*
Correspondence to: Dr J. K. Cleal, The Institute of Developmental Sciences, Southampton General Hospital, University of Southampton, MP 887, Tremona Road, Southampton SO16 6YD, Hampshire, UK. (Email [email protected])

Abstract

An appropriate foetal cardiovascular (CV) response to reduced substrate supply (e.g. oxygen or other nutrients) is vital for growth and development, and may impact on CV control. The prevailing nutritional environment and associated CV changes may influence subsequent CV responses to challenges during late gestation, for example, umbilical cord occlusion (UCO). We investigated the effect of low-circulating glucose on foetal CV control mechanisms and response to UCO. Under general anaesthesia, late gestation foetal sheep (n = 7, 119 days gestational age (dGA), term ∼147 days) were implanted with vascular catheters, a bladder catheter, electrocardiogram electrodes and an umbilical cord occluder. Mean arterial pressure (MAP), heart rate (HR) and kidney function were monitored during maternal saline (MSAL, 125dGA) and insulin (MINS, 126dGA) infusion, and foetal CV responses were assessed during incremental doses of angiotensin II, a 90-s total UCO, and administration of phenylephrine to assess baroreflex function. During MINS infusion, the decrease in maternal and foetal blood glucose was associated with a small but significant decrease in foetal HR and reduced foetal baroreflex sensitivity (P < 0.05). The increase in foetal MAP during a 90-s UCO was greater during hypoglycaemia (P < 0.05). The MAP response to angiotensin II was not affected by hypoglycaemia. Decreased foetal HR and baroreflex sensitivity and increased CV responsiveness to UCO during hypoglycaemia indicates altered CV homoestatic mechanisms. The combination of altered nutrition and a CV challenge, such as UCO, during late gestation may have a cumulative effect on foetal CV function.

Type
Original Article
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2009

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References

1.Giussani, DA, McGarrigle, HH, Spencer, JA, et al. Effect of carotid denervation on plasma vasopressin levels during acute hypoxia in the late-gestation sheep fetus. J Physiol. 1994; 477, 8187.CrossRefGoogle ScholarPubMed
2.Richardson, B, Korkola, S, Asano, H, et al. Regional blood flow and the endocrine response to sustained hypoxemia in the preterm ovine fetus. Pediatr Res. 1996; 40, 337343.CrossRefGoogle ScholarPubMed
3.Milley, JR. Effect of insulin on the distribution of cardiac output in the fetal lamb. Pediatr Res. 1987; 22, 168172.CrossRefGoogle ScholarPubMed
4.Stonestreet, BS, Boyle, LD, Papparella, A, et al. Circulatory and metabolic effects of alpha-adrenergic blockade in the hyperinsulinemic ovine fetus. J Soc Gynecol Investig. 1996; 3, 241249.CrossRefGoogle ScholarPubMed
5.Burrage, DM, Braddick, L, Cleal, JK, et al. The late gestation fetal cardiovascular response to hypoglycaemia is modified by prior peri-implantation undernutrition in sheep. J Physiol. 2009; 587, 611624.CrossRefGoogle ScholarPubMed
6.Edwards, LJ, McMillen, IC. Maternal undernutrition increases arterial blood pressure in the sheep fetus during late gestation. J Physiol. 2001; 533, 561570.CrossRefGoogle ScholarPubMed
7.Burrage, D, Green, LR, Moss, TJ, et al. The carotid bodies influence growth responses to moderate maternal undernutrition in late-gestation fetal sheep. BJOG. 2008; 115, 261268.CrossRefGoogle ScholarPubMed
8.Dawes, GS, Lobb, MO, Mandruzzato, G, et al. Large fetal heart rate decelerations at term associated with changes in fetal heart rate variation. Am J Obstet Gynecol. 1993; 168, 105111.CrossRefGoogle ScholarPubMed
9.Gardner, DS, Fletcher, AJ, Bloomfield, MR, et al. Effects of prevailing hypoxaemia, acidaemia or hypoglycaemia upon the cardiovascular, endocrine and metabolic responses to acute hypoxaemia in the ovine fetus. J Physiol. 2002; 540, 351366.CrossRefGoogle ScholarPubMed
10.Wallingford. AFRC. Energy and Protein Requirements of Ruminants. An advisory manual prepared by the AFRC technical committee on responses to nutrients. 1993. CAB International, UK.Google Scholar
11.McPherson, EA, Luo, Z, Brown, RA, et al. Chymase-like angiotensin II-generating activity in end-stage human autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2004; 15, 493500.CrossRefGoogle ScholarPubMed
12.Leury, BJ, Chandler, KD, Bird, AR, et al. Effects of maternal undernutrition and exercise on glucose kinetics in fetal sheep. Br J Nutr. 1990; 64, 463472.CrossRefGoogle ScholarPubMed
13.Giussani, DA, Spencer, JA, Moore, PJ, et al. Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep. J Physiol. 1993; 461, 431449.CrossRefGoogle ScholarPubMed
14.Peeters, LL, Sheldon, RE, Jones, MD Jr, et al. Blood flow to fetal organs as a function of arterial oxygen content. Am J Obstet Gynecol. 1979; 135, 637646.CrossRefGoogle ScholarPubMed
15.Giussani, DA, Riquelme, RA, Moraga, FA, et al. Chemoreflex and endocrine components of cardiovascular responses to acute hypoxemia in the llama fetus. Am J Physiol. 1996; 271, R73R83.Google ScholarPubMed
16.Giussani, DA, Spencer, JA, Moore, PJ, et al. Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep. J Physiol. 1993; 461, 431449.CrossRefGoogle ScholarPubMed
17.Pardal, R, Lopez-Barneo, J. Low glucose-sensing cells in the carotid body. Nat Neurosci. 2002; 5, 197198.CrossRefGoogle ScholarPubMed
18.Nurse, CA. Neurotransmission and neuromodulation in the chemosensory carotid body. Auton Neurosci. 2005; 120, 19.CrossRefGoogle ScholarPubMed
19.Alvarez-Buylla, R, Alvarez-Buylla, ER. Carotid sinus receptors participate in glucose homeostasis. Respir Physiol. 1988; 72, 347359.CrossRefGoogle ScholarPubMed
20.Alvarez-Buylla, R, de Alvarez-Buylla, E. Changes in blood glucose concentration in the carotid body-sinus modify brain glucose retention. Brain Res. 1994; 654, 167170.CrossRefGoogle ScholarPubMed
21.Koyama, Y, Coker, RH, Stone, EE, et al. Evidence that carotid bodies play an important role in glucoregulation in vivo. Diabetes. 2000; 49, 14341442.CrossRefGoogle ScholarPubMed
22.Hawkins, P, Steyn, C, Ozaki, T, et al. Effect of maternal undernutrition in early gestation on ovine fetal blood pressure and cardiovascular reflexes. Am J Physiol Regul Integr Comp Physiol. 2000; 279, R340R348.CrossRefGoogle ScholarPubMed
23.Polson, JW, Dampney, RA, Boscan, P, et al. Differential baroreflex control of sympathetic drive by angiotensin II in the nucleus tractus solitarii. Am J Physiol Regul Integr Comp Physiol. 2007; 293, R1954R1960.CrossRefGoogle ScholarPubMed
24.Green, LR, Kawagoe, Y, Homan, J, et al. Adaptation of cardiovascular responses to repetitive umbilical cord occlusion in the late gestation ovine fetus. J Physiol. 2001; 535, 879888.CrossRefGoogle ScholarPubMed
25.Giussani, DA, Spencer, JA, Moore, PJ, et al. Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep. J Physiol. 1993; 461, 431449.CrossRefGoogle ScholarPubMed
26.Somers, VK, Mark, AL, Abboud, FM. Potentiation of sympathetic nerve responses to hypoxia in borderline hypertensive subjects. Hypertension. 1988; 11, 608612.CrossRefGoogle ScholarPubMed
27.Green, LR, Kawagoe, Y, Fraser, M, et al. Activation of the hypothalamic-pituitary-adrenal axis with repetitive umbilical cord occlusion in the preterm ovine fetus. J Soc Gynecol Investig. 2000; 7, 224232.CrossRefGoogle ScholarPubMed
28.Liggins, GC. The role of cortisol in preparing the fetus for birth. Reprod Fertil Dev. 1994; 6, 141150.CrossRefGoogle ScholarPubMed
29.Nyirenda, MJ, Lindsay, RS, Kenyon, CJ, et al. Glucocorticoid exposure in late gestation permanently programs rat hepatic phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and causes glucose intolerance in adult offspring. J Clin Invest. 1998; 101, 21742181.CrossRefGoogle ScholarPubMed