Efeitos da dislipidemia materna sobre os níveis de pressão arterial, controle cardiorrespiratório e parâmetros bioquímicos na prole de fêmeas

Abstract

High blood pressure evidenced in adult rats exposed to maternal dyslipidemia may be sex dependent. In this work, we investigate the effects of dyslipidemia during pregnancy and lactation on cardiorespiratory and metabolic parameters in female offspring. Rats were divided into two groups: one received a control diet (CTL) and another received dyslipidemic diet (DLP) during pregnancy and lactation. Anthropometric and biochemical parameters were performed in the pups of these rats at 30 and 90 days of age, such as: weight and length of offspring, oral glucose tolerance (OGT), insulin tolerance (IT), total cholesterol (TC) tests, high (HDL), low (LDL) and very low density (VLDL) lipoproteins, triglycerides (TG), and malondialdehyde (MDA). In addition, respiratory parameters such as respiratory frequency (RF), tidal volume (VT), and minute ventilation (VE) were assessed by whole body plethysmography during a baseline period and after activation of hypercapnic mixture (7% CO2) respiratory chemoreceptors. At 90 days of age, blood pressure (BP) and heart rate (HR) were measured under basal conditions and after administration of potassium cyanide (KCN, 0.04%) to evaluate peripheral chemoreflex, and hexamethonium (30 mg / kg) to assess sympathetic tone. Finally, we evaluated the HR and BP variability under baseline conditions. The DLP group had low birth weight (P<0.05), but without differing weight in adulthood. At 30 days of age, serum TG and TC levels were increased in DLP offspring (P<0.05). DLP females also had an increase in basal RF, and a higher ventilatory response to hypercapnia compared to the CTL group (P<0.05). At 90 days, the DLP offspring presented larger area under the curve in OTG and IT compared to CTL group. At baseline, RF, VT, VE were similar between groups, but DLP offspring had a high cardiovascular and ventilatory response to hypercapnia when compared to CTL group (P<0.0001). The blood pressure levels of the DLP rats were high (P<0.05), but without change in HR. In the spectral analysis, it was observed that the LF component of systolic BP and the LF / HF ratio of cardiac interval were elevated in the DLP group (P<0.05). The pharmacological challenges imposed by the KCN revealed higher pressure response of the DLP group (P<0.05) but without altering the HR delta. After hexamethonium administration, DLP females showed a tendency to sympathetic tone (P<0.06). These findings were combined with elevated serum MDA levels (P<0.05). The offspring of DLP rats presented arterial hypertension in adulthood combined with sympathetic hyperactivity and amplified ventilatory and autonomic responses to hypoxia and hypercapnia.