Increased blood pressure in the offspring of diabetic mothers

Abstract

Studies were conducted in rats to determine the effect of maternal diabetes and the consequent hyperglycemia on cardiovascular function in the offspring. Diabetes was induced in pregnant Wistar rats through streptozotocin injection (50 mg/kg). Cardiovascular parameters were measured in 2-mo-old offspring animals of diabetic (OD, n ϭ 12) and control rats (OC, n ϭ 8). Arterial pressure (AP), heart rate (HR), baroreflex sensitivity, and vascular responsiveness to phenylephrine (PH) and sodium nitroprusside (SN) were measured. Angiotensinconverting enzyme (ACE) activity in heart, kidney, and lung was determined. OD rats exhibited increases in systolic AP (138 Ϯ 8 vs. 119 Ϯ 6 mmHg, OD vs. OC), with no change in HR (342 Ϯ 21 vs. 364 Ϯ 39 beats per minute (bpm), OD vs. OC). The reflex tachycardia elicited by SN was reduced in OD rats, as indicated by the slope of the linear regression (Ϫ2.2 Ϯ 0.4 vs. Ϫ3.6 Ϯ 0.8 bpm/mmHg, OD vs. OC). Vascular responsiveness to PH was increased 63% in OD rats compared with OC. OD rats showed increases in ACE activity in heart, kidney, and lung (1.13 Ϯ 0.24, 3.04 Ϯ 0.86, 40.8 Ϯ 8.9 vs. 0.73 Ϯ 0.19, 1.7 Ϯ 0.45, 28.1 Ϯ 6 nmol His-Leu ⅐ min Ϫ1 mg protein Ϫ1 , OD vs. OC). Results suggest that diabetes during pregnancy affects cardiovascular function in offspring, seen as hypertension, baroreflex dysfunction, and activation of tissue renin-angiotensin system. cardiovascular; heart rate; development; angiotensin-converting enzyme; renin-angiotensin system; hyperglycemia EVIDENCE SUGGESTS THAT THE mother's lifestyle may have longlasting effects on offspring. For example, smoking, alcohol consumption, and presence of disease states such as diabetes and hypertension during pregnancy all affect fetal development (8,27). Alterations in fetal development could contribute to pathologies in the adult. With regard to diabetes, even when treated, the maternal disease has profound consequences on the fetus, seen as changes in brain, pancreas, lung, kidney, and heart (2, 14, 21, 44).To study diabetes in the experimental setting, chemical toxins have been widely used. Streptozotocin (STZ) is a pancreatic toxin that induces hyperglycemia, hypoinsulinemia, polyuria, and weight loss in rats (9,28,38,45). When STZinduced hyperglycemia is present during pregnancy, there are changes in fetal development and metabolism, including growth restriction and abnormal pancreatic function (5, 22, 36). Epidemiological and animal studies have shown that low birth weight increases the incidence of cardiovascular disease and diabetes mellitus in adulthood (3). Intrauterine growth restriction produced by placental insufficiency in pregnant rats was associated with marked elevation in blood pressure of the offspring (1). Adult offspring of STZ-diabetic rats also showed signs of cardiovascular dysfunction, seen as a reduced response to endothelium-dependent vasodilators and enhanced norepinephrine-induced vasoconstriction (23).There is evidence for an association between the development of diabetes and the activation of the reni...

Effect of sodium overload on renal function of offspring from diabetic mothers

“…This is in agreement with the results shown by Wichi et al [9], Magaton et al [10], and Rocha et al [12]. Salt overload beginning after weaning, as expected, also resulted in hypertension.…”

“…Experimental and clinical studies have demonstrated that sustained exposure of the fetus to elevated concentrations of glucose increases the risk of intrauterine death, prematurity, perinatal mortality, and congenital malformations [4][5][6]. Increased risk for cardiovascular diseases and diabetes has been observed in the offspring of diabetic mothers at adulthood [7][8][9].…”

Evidence for Sympathetic Origins of Hypertension in Juvenile Offspring of Obese Rats

“…The MAP-HR relationship was reset toward higher pressure (rightward shift). Resetting of the baroreflex has been reported in other models of developmental programming; prenatal exposure to dexamethasone in sheep 30 or nutrition restriction in rat 31 has been shown to lead to a blunted baroreflex control of HR in adulthood, and Wichi et al 32 have demonstrated impaired baroreflex tachycardia elicited by decreasing MAP in offspring of streptozotocin-induced diabetic rats. However, the resetting of the baroreflex is commonly a consequence of hypertension 33 but has also been implicated in the development of hypertension.…”

Maternal Diabetes Increases Small Conductance Ca2+-Activated K+(SK) Currents That Alter Action Potential Properties and Excitability of Cardiac Motoneurons in the Nucleus Ambiguus

“…In the autonomic nervous system, maternal diabetes impairs sympathetic and parasympathetic development in offspring (Fiorentini et al 2005;Young and Morrison 1998). Recently Wichi et al (2005) found that maternal diabetes impairs baroreflex control of heart rate (HR) in offspring of STZ-induced diabetic mothers. Because attenuation of baroreflex sensitivity is associated with many cardiovascular diseases including sudden death (La Rovere et al 2008), it is critically important to study the effects of maternal diabetes on the neural components within the baroreflex circuitry.…”