Abstract P3041: Maternal Hypertension Sensitizes Post Weaning High Fat Diet Elicited Hypertension in Adult Offspring

Abstract

Our previous studies showed that maternal hypertension sensitizes angiotensin (ANG) II-induced hypertension and this sensitization is associated with upregulation of renin-angiotensin system (RAS) components and proinflammatory cytokines (PICs) in the brain cardiovascular nuclei. In this study, we investigated whether the offspring from mothers with maternal hypertension had a sensitized hypertensive response elicited by high-fat diet (HFD) feeding for 12 weeks beginning from the time of weaning. In both male and female offspring, basal mean arterial pressure (MAP) in normal-fat diet (NFD) feeding offspring of either normotensive (NT; males, 112.3±2.2; females, 109.0±1.5 mmHg) or hypertensive (HT; males 112.4±1.0; females 108.4±1.3 mmHg) dams were comparable. HFD feeding significantly elevated MAP in both male and female offspring. However, the increases in MAP were greater in offspring of HT dams (males, 128.0±2.3 mmHg; females, 121.0±1.8 mmHg) than that in the offspring of NT dams (males, 120.8±1.4 mmHg; females, 115.3±1.2 mmHg). Ganglionic blockade (hexamethonium, ip) produced a greater reduction fall in MAP only in male HFD-fed offspring when compared to NFD-fed offspring of either NT dams (-45.2±3.4 vs. -20.9±4.1 mmHg) or HT dams (-41.2±6.7 vs. -26.6±2.5 mmHg), suggesting that HFD feeding elicited an increased sympathetic tone in males, but not in females. In lamina terminalis tissues, RT-PCR analyses revealed that HFD feeding in both male and female offspring of HT dams led to a significant increase in mRNA expression of several components of the RAS and PICs (males, leptin, ACE, NOX2 and TNF-α; females, leptin, AT1R, NOX2 and TNF-α). However, maternal hypertension resulted in a significant increase in mRNA expression of leptin and AT1R only in male offspring fed NFD when compared with NFD offspring of NT dams. The results indicate that maternal hypertension sensitized HFD-elicited HT in both male and female adult offspring, but in a sex-specific manner associated with altered sympathetic tone and expression of RAS components and PICs in the brain.