Parental Obesity Alters Offspring Blood Pressure Regulation and Cardiovascular Responses to Stress: Role of P2X7R and Sex Differences.

The prevalence of obesity has increased dramatically in the United States during the past three decades. This increase has occurred in children, adolescents and adults of both sexes and all ethnic groups. In addition, the proportion of women and men of reproductive age who are overweight and obese has been increasing considerably, and maternal obesity and excessive gestational weight gain may predispose their offspring to health-related consequences during childhood and adulthood, and increase cardiovascular responses to stress. Therefore, we examined the impact of parental (maternal + paternal) obesity on offspring blood pressure (BP) regulation and cardiovascular responses to stress. Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN, n=5 per sex) or a high fat (H) diet (NH, n=5-7 per sex) from weaning until adulthood. Offspring from obese H diet-fed parents were also fed N (HN, n=5-6 per sex) or H diet (HH, n=5-8 per sex). Body weight, calorie intake and fat mass were measured at 22 weeks of age when cardiovascular phenotyping was performed. Male and female HH offspring were 15% heavier than NH and 70% heavier than NN offspring. Male HH and HN offspring had elevated BP (121±2 and 115±1 mmHg, by telemetry) compared to male NH and NN offspring (108±6 and 107±3 mmHg, respectively) and augmented BP response to angiotensin II, losartan and hexamethonium. Male HH and HN offspring also showed increased BP response to acute air-jet stress (37±2 and 38±2 mmHg) compared to only 24±3 and 25±3 mmHg in NH and NN offspring. Baseline heart rate (HR) and HR responses to air-jet stress were similar among groups. In females, BP and cardiovascular responses to stress were similar among all offspring. Male H diet-fed offspring from obese H diet-fed purinoreceptor 7 deficient (HH-P2X7R-KO) parents had normal BP that was similar to control NN-P2X7R-KO offspring from lean parents. These results indicate that parental obesity leads to increased BP and augmented BP response to stress in their offspring in a sex-dependent manner and that the impact of parental obesity on male offspring BP regulation is markedly attenuated in P2X7R-KO mice.