Role of the sympathetic nervous system in the development of hypertension and metabolic syndrome in low birth weight offspring
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The sympathetic nervous system plays a pivotal role in the development of the metabolic syndrome particularly hypertension in low birth weight offspring. The Barker hypothesis reported that individuals born with low birth weight were at risk of developing chronic diseases later in life. Animal and human studies have since confirmed this relationship, however the mechanisms involved remain unknown. Therefore, this study investigated the role of the sympathetic nervous system in protein restricted rats and pre-clinical University of Zimbabwe students whose birth weights were less than 2.5kg. According to the Barker hypothesis adverse influences early in foetal development can result in permanent changes in the metabolism and physiology with such changes resulting in increased disease risk of the metabolic syndrome in adulthood. It was hypothesized that the sympathetic nervous system was the mechanism by which themetabolic syndrome particularly hypertension occurred in low birth weight and intrauterine growth restricted offspring. An intrauterine growth restricted (IUGR) rat model was developed using local Zimbabweans diets. Using this model, mean blood pressure (mmHg) measured using the tail cuff method was significantly higher within 10 weeks in IUGR rats than in normal rats (122.46±2.73 vs 106.50±5.81 p=0.0001). The blood pressure significantly decreased in IUGR rats whose renal nerve (sympathetic influence) had been denervated (103.44±8.17mmHg vs 98.49±7.85mmHg p=0.013). A series of human experiments were then conducted in young adults from the University of Zimbabwe. The students were put through exercise paces to allow the expression of the autonomic nervous system. Heart Rate Variability (HRV) ratio, and Pulse Wave Amplitude (PWA) responses to activation of the muscle metaboreflex were exaggerated in low birth weight (LBW) compared to normal birth weight (NBW) offspring (HRV: 1.015±1.034 vs 0.119±0.789 p<0.05) PWA: -1.320±1.064 vs -0.735±0.63 mV p=0.28. This suggested that the exercise pressor reflex, which is involved in tight regulation of the cardiovascular response to exercise, is persistently dysregulated into early adulthood for LBW individuals. The study showed a significant difference in decrease in diastolic function (E/A ratio) in LBW than NBW groups ( 0.48±0.27 vs 0.19±0.18 p=0.031) and a significant association between LBW and exercise induced cardiac fatigue with diastolic dysfunction (p<0.001 odds risk ratio 7.5[95% CI 2.7-20.7]). Furthermore, the mechanisms of exercise induced cardiac fatigue involved transient myocardial stunning and a decrease in sensitivity of myocardium to catecholamines reducing the effect of adrenaline in improving both systolic and diastolic function during exercise. LBW was associated with exercise induced hypertension (EIH) (62% vs 32% p<0.05) and post exercise hypotension (PEH) in young adults, a phenomenon hypothesised to be mediated by two processes; physiological down regulation of the cholinergic sympathetic vasodilator receptors in peripheral tissues due to chronic sympathetic stimulation; and increased wall thickening (EIH) and derangements in sympathetic tone (PEH). In the glucose tolerance study in LBW young adults had elevated sympathetic activity and were glucose intolerant (after 60mins 8.4±.56 mmol/l vs 7.57±0.36mmol/l p=0.035). It is concluded that the sympathetic nervous system possibly has a role in the development of the metabolic syndrome in low birth weight humans and intrauterine growth restricted rats.
Additional Citation InformationChifamba, J. (2015). Role of the sympathetic nervous system in the development of hypertension and metabolic syndrome in low birth weight offspring. (Unpublished Doctoral thesis). University of Zimbabwe.
SponsorNational Institute of Neurological Disorders and Stroke (NINDS). Office of the Director -National Institutes of Health (OD) and National Heart, Lung, And Blood Institute (NHLBI) through a Medical Education Partnership Initiative (MEPI) Grant to the University of Zimbabwe College of Health Sciences and Southern Africa Consortium for Research Excellence (SACORE) and the University of Zimbabwe College of Health Sciences Physiology Department.
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