Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and sensitization of angiotensin II-induced hypertension in adult offspring

Abstract

Accumulating evidence indicates that maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular disease in adult offspring. The present study tested the hypothesis that maternal HFD modulates the brain renin-angiotensin system (RAS), oxidative stress, and proinflammatory cytokines that alter angiotensin II (ANG II) and TNF-α actions and sensitize the ANG II-elicited hypertensive response in adult offspring. All offspring were cross fostered by dams on the same or opposite diet to yield the following four groups: offspring from normal-fat control diet-fed dams suckled by control diet-fed dams (OCC group) or by HFD-fed dams (OCH group) and offspring from HFD-fed dams fed a HFD suckled by control diet-fed dams (OHC group) or by HFD-fed dams (OHH group). RT-PCR analyses of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAS components, NADPH oxidase, and proinflammatory cytokines in 10-wk-old male offspring of dams fed a HFD during either pregnancy, lactation, or both (OHC, OCH, and OHH groups). These offspring also showed decreased cardiac baroreflex sensitivity and increased pressor responses to intracerebroventricular microinjection of either ANG II or TNF-α. Furthermore, chronic systemic infusion of ANG II resulted in enhanced upregulation of mRNA expression of RAS components, NADPH oxidase, and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented hypertensive response in the OHC, OCH, and OHH groups compared with the OCC group. The results suggest that maternal HFD blunts cardiac baroreflex function and enhances pressor responses to ANG II or proinflammatory cytokines through upregulation of the brain RAS, oxidative stress, and inflammation. NEW & NOTEWORTHY The results of our study indicate that a maternal high-fat diet during either pregnancy or lactation is sufficient for perinatal programming of sensitization for hypertension, which is associated with hyperreactivity of central cardiovascular nuclei that, in all likelihood, involves elevated expression of the renin-angiotensin system, NADPH oxidase, and proinflammatory cytokines. The present study demonstrates, for the first time, the central mechanism underlying maternal high-fat diet sensitization of the hypertensive response in adult offspring.

Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta‐analysis of animal studies

“…Blood pressure was measured via a tail cuff ( N = 6 studies) or invasively by remote radio‐telemetry after surgical implantation of carotid artery probes ( N = 5 studies) . Effect estimates did not differ substantially between both methods.…”

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

“…ACE cleaves angiotensin I to form angiotensin II, a potent regulator of vascular function and blood volume (Dasinger et al 2016). In rodents, offspring of dams fed diets high in fat (Zhang et al 2018) and salt (Mao et al 2013) or low in protein (Watkins et al 2010) have all been shown to program offspring cardiovascular dysfunction via impaired RAS regulation.…”

Maternal high-fat diet triggers metabolic syndrome disorders that are transferred to first and second offspring generations

“…In addition, the baroreflex presents two components, the tachycardic that represents sympathetic activity and the bradycardic that represents parasympathetic activity (42,43) . In the Zhang et al (41) study, only reflex tachycardia was evaluated, whereas in the present study only reflex bradycardia was evaluated. The sympathetic dysfunction was evidenced in our present study and suggests a dysfunction in the reflex tachycardia according to data from Zhang et al (41) .…”

“…The increase in basal MAP in F1H and F2H offspring are consistent with the previous studies where female genitors were fed H diet for long-term, including before pregnancy until lactation (38)(39)(40) . According to Zhang et al (41) , female rats fed a H diet for 2 weeks before pregnancy until lactation showed no changes in basal MAP and blunted tachycardia baroreflex sensitivity in the F1H offspring. The difference in the basal MAP observed between our present study and Zhang et al study (41) may be due to the differential age of the F1H offspring.…”

“…According to Zhang et al (41) , female rats fed a H diet for 2 weeks before pregnancy until lactation showed no changes in basal MAP and blunted tachycardia baroreflex sensitivity in the F1H offspring. The difference in the basal MAP observed between our present study and Zhang et al study (41) may be due to the differential age of the F1H offspring. In addition, the baroreflex presents two components, the tachycardic that represents sympathetic activity and the bradycardic that represents parasympathetic activity (42,43) .…”