Streptozotocin diabetes in the pregnant rat induces cardiovascular dysfunction in adult offspring

Abstract

Severe diabetes in pregnant rats produces persistent metabolic consequences in adult offspring. This study investigated whether diabetes in pregnant rats could also lead to cardiovascular abnormalities in the adult offspring. Blood pressure, heart rate and in vitro vascular reactivity of small arteries were evaluated in female adult offspring of control rats and of rats rendered diabetic with streptozotocin. Rise in blood pressures were similar in both groups of offspring but heart rate was lower in the diabetic offspring (p < 0.05). The rise in blood pressure associated with infusion of a nitric oxide synthase inhibitor was similar in both groups, but the associated decrease in heart rate was more pronounced in diabetic offspring (p < 0.01). Small mesenteric arteries from this group showed enhanced sensitivity to noradrenaline (p < 0.05) and abnormal endothelium-dependent relaxation to acetylcholine (p < 0.01) and bradykinin (p < 0.05). Reduction in acetylcholine induced relaxation, reflected reduced synthesis of nitric oxide or a cyclooxygenase product and was not attributable to an endothelium-derived hyperpolarizing factor. Sensitivity to exogenous nitric oxide was normal. A subgroup of pups born to diabetic dams were suckled by control maternal dams and a subgroup of those born to controls by diabetic dams. Suckling was an important determinant of impaired growth; offspring of diabetic rats suckled by their own mother and those of control rats by diabetic dams showed impaired growth rates whereas growth of offspring of diabetic rats suckled by control dams paralleled those of control rats suckled by their own mother.