Foetal Programming In Blood Pressure Regulation

ABDULKAREEM, Toyyib Oladimeji

Presentation by:

Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin.

Outline Introduction Blood pressure Foetal programming Foetal programming in blood pressure regulation Summary Conclusion References

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Definition of terms Blood Pressure = BP Systolic Blood Pressure = SBP Diastolic Blood Pressure = DBP Autonomic Nervous System = ANS World Health Organization = WHO Gestational Diabetes Mellitus = GDM Low Birth Weight = LBW Intrauterine Growth Restriction = IUGR Uteroplacental Insufficiency = UPI Peripheral Resistance = PR Metabolic Syndrome = MetS 11-β-Hydroxysteroid Dehydrogenase type 2 = 11-Β-HSD2 3

INTRODUCTION Foetal programming

may be defined as the phenomenon whereby a stimulus that occurs during a critical window of development can bring about lifelong changes in bodily structure and function (Blondeau et al., 2010).

Insults during the foetal period predispose the offspring to various diseases and anomalies.

BP is the pressure exerted by circulating blood upon the walls of blood vessels normal = 120/80 mmHg.

FIGURE 1: Dutch Famine of 1944 – Universiteit leiden

FIGURE 2: Biafra famine – Igbo focus4

FOETAL PROGRAMMING The Barker Hypothesis, states that conditions during pregnancy will have long term

effects on adult health. Conditioning by a “Poor Start to Life” Conditioning by over nutrition - both maternal obesity and GDM have been

implicated in leading to a later risk of obesity and cardiometabolic disease risk in the offspring (Lawlor et al., 2004; Reynolds et al., 2013).

FIGURE 3: Prof David JP Barker, 2012; lifecourse epidemiology.

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PHYSIOLOGIC PATHWAYS

FIGURE 4: Physiological adaptive processes in developmental conditioning - Hanson and Gluckman, 2014; Early developmental conditioning of later health and disease: physiology or pathophysiology 6

PATHOPHYSIOLOGICAL PATHWAYS

FIGURE 5: Pathophysiological non-adaptive processes in developmental conditioning - Hanson and Gluckman, 2014; Early developmental conditioning of later health and disease: physiology or pathophysiology 7

BLOOD PRESSURE BP is the pressure exerted by circulating blood upon the walls of blood vessels Age, sex, resistance, conductance, life style, blood vessels affects BP Mean arterial pressure = 1/3 SBP + 2/3 DBP, 93.33mmHg

TABLE 1: Various category of blood pressure

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MEASUREMENT OF BLOOD PRESSURE NONINVASIVE – palpation (carotid, femoral, radial pulses)

– auscultation (stethoscope and sphygmomanometer)

– oscillometric (oscillations of blood flow) INVASIVE - most accurately measured invasively through an arterial line.

FIGURE 6: Pulse palpation, Weinberg 2011, Vascular medicine

FIGURE 7: Auscultatory technique for measuring blood pressure - Applegate, 20009

REGULATION OF BLOOD PRESSURE BARORECEPTOR REFLEX - A

baroreceptor is a sensory receptor that responds to pressure.

Baroreceptor medulla ANS (heart and PR) RENAL CONTROL - Rising pressure

causes the kidneys to excrete the excess volume, thus returning the pressure back toward normal and vice versa when pressure falls.

Hypothalamic pituitary adrenal (HPA) axis – CRH, ACTH, Aldosterone release

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM - raises arterial pressure in several ways.

FIGURE 8: Renin-angiotensin vasoconstrictor mechanism for arterial pressure control (Guyton and Hall, Textbook of medical physiology, 2013, Saunders company).

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ABNORMAL BLOOD PRESSURE

HYPOTENSION - Blood pressure that is too low is known as hypotension.

FIGURE 10: Effects of hypertension, Harvard Health Publication

►HYPERTENSION - Hypertension is a sustained elevation of blood pressure.

FIGURE 9: Signs or Symptoms of hypotension, National Heart Lung and Blood Institute, 2008. 11

FOETAL PROGRAMMING IN BLOOD PRESSURE REGULATION Prenatal influences on these have been explored as potential mechanisms

through which fetal nutritional insufficiency affects long-term blood pressure.

Offspring blood pressure is elevated by insults like;

- Fetal growth restriction (Langley-Evans et al., 1999; Vehaskari et al., 2001; Woods et al., 2001; Battista et al., 2002)

- Administration of corticosteroids during pregnancy (Dodic et al., 2002)

- Manipulation of uterine blood supply (Alexander, 2003)

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Foetus InsultsAdaptive and non-adaptive changes in the foetus

Impairment of BP regulation

Low Birth Weight and Blood Pressure Regulation LBW, defined as birth weight of <2500g by the WHO, may arise from IUGR, or

prematurity (Zandi-Nejad et al., 2006)

Several animal models have demonstrated the inverse relationship between LBW and hypertension (Manning et al., 2001; Poladia et al., 2006)

FIGURE 11: A comparison between normal and IUGR babies - Lausman et al., 2012; Screening, Diagnosis and Management of IUGR; Journal of Obstetrics & Gynecology. 13

Glucocorticoids and programming of blood pressure A single course of antenatal corticosteroid is associated with higher

blood pressure in adolescence and decreased insulin sensitivity and renal function in adulthood (Doyle et al., 2000; Seckl et al., 2007).

This restricts fetal growth and program permanent changes in the cardiovascular, endocrine, and metabolic systems (Edwards et al., 2001).

11-β-HSD2 inactivates glucocorticoids to their inert 11-keto forms (cortisone).

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15FIGURE 12: Feotal programming and blood pressure - Norma et al., 2008; Role of Fetal Programming in the Development of Hypertension, Future Cardiol.

Glucocorticoids and other insults

OTHER METHODS Sexual Dimorphism and blood pressure programming -

estrogen play a protective role (Ojeda et al., 2007).

males appear to be much more sensitive to insult in utero (Grigore et al., 2008).

Maternal health and blood pressure programming - epidemiological studies have clearly identified maternal health as a major factor for the development of MetS in offspring (Fetita et al., 2006).

Neonatal oxygen exposure and blood pressure programming - premature newborns are more susceptible to oxidative tissue damage (Hardy et al., 2000; Thebaud et al., 2005).

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Summary Insults are bad for the unborn child. They cause the child to have

developmental changes including BP regulation. Numerous studies have largely supported blood pressure

programming and serve to illustrate complexity of the maternal-fetal-environmental interaction.

Conclusion The goal of pregnancy is to have a healthy baby. People should be

be careful of insults as they can lead to impairment of BP regulation in the unborn child.

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For Listening !!! 18

REFERENCES Alexander, B.T. (2003). Placental insufficiency leads to development of hypertension in

growth-restricted offspring. Hypertension 41:457–62. Bateson, P. and Gluckman, P. (2011). Plasticity, Robustness, Development and Evolution.

Cambridge, UK: Cambridge Univ. Press. Blondeau, B., Joly, B., Perret, C., Prince, S., Bruneval, P., Lelièvre-Pégorier,

M., Fassot, C. and Duong Van Huyen, J.P. (2011). Exposure in utero to maternal diabetes leads to glucose intolerance and high blood pressure with no major effects on lipid metabolism, Diabetes &amp; Metabolism Volume 37, n° 3 pages 245-251.

Dodic, M., Moritz, K., Koukoulas, I. and Wintour, E.M. (2002). Programmed hypertension: kidney, brain or both? Trends Endocrinol. Metab. 13:403–8.

Edwards, L.J., Coulter, C.L., Symonds, M.E. and McMillen, I.C. (2001). “Prenatal under nutrition, glucocorticoids and the programming of adult hypertension,” Clinical and Experimental Pharmacology and Physiology, vol. 28, no. 11, pp. 938–941.

Harding, J.E. (2001). The nutritional basis of the fetal origins of adult disease. Int. J. Epidemiol. 30:15–23.

Lawlor, D.A., Najman, J.M., Sterne, J., Williams, G.M., Ebrahim, S. and Davey, S.G. (2004). Associations of parental, birth, and early life characteristics with systolic blood pressure at 5 years of age: findings from the Mater-University study of pregnancy and its outcomes. Circulation 110: 2417–2423. 19

REFERENCES Ojeda, N.B., Grigore D., Robertson E.B. and Alexander B.T. (2007). “Estrogen protects

against increased blood pressure in post pubertal female growth restricted offspring,” Hypertension, vol. 50, no. 4, pp. 679–685.

Poladia D.P., Kish K., Kutay B., Bauer J., Baum M., and Bates C.M. (2006). “Link between reduced nephron number and hypertension: studies in a mutant mouse model,” Pediatric Research, vol. 59, no. 4, pp. 489–493.

Reynolds R.M., Allan K.M., Raja E.A., Bhattacharya S., McNeill G., Hannaford P.C., Sarwar N., Lee A.J., Bhattacharya S., and Norman J.E. (2013). Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 323 275 person years. BMJ 347: f4539.

Seckl J.R. and Holmes M.C. (2007). Mechanisms of disease: glucocorticoids, their placental metabolism and fetal ‘programming’ of adult pathophysiology. Nat Clin Pract Endocrinol Metab. 3:479–488.

Thebaud B., Ladha F., Michelakis E.D., Sawicka M., Thurston G., Eaton F., Hashimoto K., Harry G., Haromy A., Korbutt G. and Archer S.L. (2005). Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization. Circulation. 112:2477–2486.

Vehaskari V.M., Aviles D.H., and Manning J. (2001). Prenatal programming of adult hypertension in the rat. Kidney Int. 59: 238–45. 20