Autonomic Dysfunction: A Potential Mechanism in Programmed Hypertension

Dissanayake H.U.W; Phang M

Autonomic Dysfunction: A Potential Mechanism in Programmed Hypertension

Dissanayake H.U.W and Phang M^*: Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Australia

^*Corresponding Author: Phang M, Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Australia, Tel: +61 2 86271924, Email: Melinda.phang@sydney.edu.au

Received: 11-Nov-2016 / Accepted Date: 12-Nov-2016 / Published Date: 16-Nov-2016

View PDF Download PDF

75475

Editorial

Hypertension, a disease of deregulation of blood pressure control, is a major risk factor for cardiovascular and cerebrovascular diseases [1] and is reported to affect approximately 40% of people [2]. In addition to the high prevalence and predicted increases incidence of hypertension, successful treatment remains poor and it has been argued that this is partly due to the poor understanding of causative mechanisms. The autonomic nervous system is central to the control of blood pressure and a neurogenic component of hypertension is becoming increasingly realised as several lines of evidence in humans and animal models show convincingly that abnormalities in autonomic control of blood pressure plays a major role in the etiology of disease and cardiovascular mortality. The mammalian nervous system begins its development during fetal life and continues after birth. Therefore, it is thought that both intrauterine and postnatal insults may sensitise and alter the development of different components of the nervous system.

There is a robust body of evidence indicating that a number of different nutritional manipulations or other adverse variations in the prenatal environment program hypertension; this has been shown convincingly in a number of animal models [3]. Whilst the resultant pathophysiology underlying programmed hypertension is uncertain and may be varied, there is evidence for autonomic dysfunction as a possible causative pathophysiological mechanism underlying the development of fetal programming of hypertension.

To date there has been limited interest in autonomic dysfunction as a potential mechanism in programmed hypertension which may be due to historical reasons as well as technical limitations associated with autonomic measurements.

Historically, the kidney was considered the sole contributor of long term blood pressure control, this theory stems from the teachings of the highly influential Guyton model of blood pressure control. Therefore, many of the work investigating programmed hypertension explored kidney dysfunction as a plausible mechanism in determining the etiology of programmed hypertension. Studies investigating the kidney have indeed shown windows of susceptibility to blood pressure programming that appear to occur during the early stages of kidney development, showing a reduction in glomeruli and nephron number [4-6]. However, there is conflicting evidence as studies show hypertension in the absence of reduced nephron number [7] and reduced nephron number with no apparent hypertension [8]. Although it is physiologically plausible that abnormalities in the kidney may be of importance to the etiology of programmed hypertension, the data indicate that while nephron deficit may play a permissive role, it is not the primary cause of programmed hypertension.

Over the last decade technological advancement have greatly improved our ability to accurately quantify or measure autonomic function. Earlier studies investigating blood pressure of programmed rats used more invasive techniques, such as tail cuff plethysmography. It has been postulated that these types of invasive techniques may be inducing a stress response and therefore the observed increased blood pressures may not be reflective of resting hypertension but that of an exaggerated stress response. Animal models have been used extensively to investigate programmed hypertension using a variety of maternal manipulations [3] however only a few have investigated autonomic dysfunction as a potential mechanism. A study by Samuelsson and colleagues [9] showed hypertension and increased sympathetic activity in rat offspring from mothers fed an obesogenic diet during pregnancy. In addition, hypertension and changes to sympathetic activity was established in the juvenile rate indicating that hypertension and changes in autonomic activity arise as a direct consequence of in utero exposure to a maternal obesogenic diet. Similarly, a study investigating a high fat diet in the absence of maternal obesity in rats showed increased sympathetic activity and blood pressure only in response to a stressor [10]. Studies in rabbits also show increased blood pressure and renal sympathetic nerve activity in offspring from mothers that were fed a high fat diet. Furthermore, an exaggerated sympathetic response was seen when these rabbits were exposed to an acute stressor [11].

Non-invasive measures of autonomic function are imperative when translating these effects into human studies. Recent techniques of heart rate variability and blood pressure variability have facilitated the exploration of autonomic dysfunction as a potential mechanism in programmed hypertension. Several studies of growth-restricted children show changes to cardiovascular control, these include altered blood pressure [12], increased pulse rate [13] and change in heart rate fluctuations [14]. Assessment of heart rate variability has shown that infants born small-for-gestational-age (SGA) exhibit increased sympathetic activity at one and three months of age compared to infants born appropriate-for-gestational age [15]. Beyond childhood, in adults born SGA, direct recording of sympathetic nerve traffic using microneurography showed increased sympathetic nerve activity compared to their control counterparts, who did not differ by central adiposity, body mass index or glucose tolerance; therefore metabolic factors did not attribute to the increased sympathetic activity seen in these SGA individuals [16]. Furthermore, a strong association between low birth weight and a shorter pre ejection period, indicative of a stronger sympathetic control of heart rate [17,18] and increased sympathetic activation of the heart has also been reported [17].

In line with these findings, studies have also shown an association between diminished parasympathetic control and increased risk of malignant cardiac arrhythmias and hypertension [19].

Young adults born with extremely low birth weight exhibit a significantly decreased parasympathetic regulatory capacity compared to their control counterparts during their second and third decade of life [19]. Collectively, these studies suggest that increased sympathetic and reduced parasympathetic activity may manifest during early development, and that autonomic dysfunction is a plausible mechanism underlying the increased risk of hypertension in individuals who had intrauterine growth restriction [16,20].

There is increasing evidence for autonomic dysfunction as a potential mechanism in programmed hypertension. However, to explore the exact mechanism by which this occurs requires further experimental investigation incorporating recent techniques in measuring autonomic function.

75499

References

Reule S, Drawz PE (2012) Heart rate and blood pressure: any possible implications for management of hypertension? Curr Hypertens Rep 14: 478-484.
Organization WH (2013) A global brief on hypertension: Silent killer, global public health crisis.
Vehaskari VM, LL (2005) Woods Prenatal programming of hypertension: lessons from experimental models. J Am Soc Nephrol 16: 2545-2556.
Ortiz LA (2001) Effect of prenatal dexamethasone on rat renal development. Kidney Int 59: 1663-1669.
Woods LL (2001) Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res 49: 460-467.
Zeman FJ (1968) Effects of maternal protein restriction on the kidney of the newborn young of rats. J Nutr 94: 111-116.
Silva DA (2003) Renin-angiotensin system function and blood pressure in adult rats after perinatal salt overload. Nutr Metab Cardiovasc Dis 13: 133-139.
Zimanyi MA, Bertram JF, Black MJ (2002) Nephron number and blood pressure in rat offspring with maternal high-protein diet. Pediatr Nephrol 17: 1000-1004.
Samuelsson AM (2010) Evidence for sympathetic origins of hypertension in juvenile offspring of obese rats. Hypertension 55: 76-82.
Rudyk O (2011) Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats. PLoS ONE 6: 25250.
Prior LJ (2014) Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits. Hypertension 63: 338-345.
Jones A (2007) Size at birth and autonomic function during psychological stress. Hypertension 49: 548-555.
Phillips DI, Barker DJ (1997) Association between low birthweight and high resting pulse in adult life: is the sympathetic nervous system involved in programming the insulin resistance syndrome? Diabetic Med 14: 673-677.
Ward AM (2004) Size at birth and cardiovascular responses to psychological stressors: evidence for prenatal programming in women. J hypertens 22: 2295-2301.
Galland BC (2006) Heart rate variability and cardiac reflexes in small for gestational age infants. J Appl Physiol 100: 933-939.
Boguszewski MC (2004) Low birth size and final height predict high sympathetic nerve activity in adulthood. J hypertens 22: 1157-1163.
IJzerman RG (2003) Low birth weight is associated with increased sympathetic activity dependence on genetic factors. Circulation 108: 566-571.
Cacioppo JT (1994) Autonomic cardiac control. II. Noninvasive indices and basal response as revealed by autonomic blockades. Psychophysiology 31: 586-598.
Mathewson KJ (2014) Reduced respiratory sinus arrhythmia in adults born at extremely low birth weight: Evidence of premature parasympathetic decline? International Journal of Psychophysiology 93: 198-203.
Gennser G, Rymark P, Isberg PE (1988) Low birth weight and risk of high blood pressure in adulthood. BMJ 296: 1498-1500.

Citation: Dissanayake H, Phang M (2016) Autonomic Dysfunction: A potential Mechanism in Programmed Hypertension. J Paediatr Lab Med 1: e101

Copyright: © 2016 Dissanayake H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

黑料网