Fructose-rich diet induces gender-specific changes in expression of the renin–angiotensin system in rat heart and upregulates the ACE/AT1R axis in the male rat aorta

Abstract

Introduction:The cardiovascular renin–angiotensin system (RAS) could be affected by gender and dietary regime. We hypothesized that male rats will be more susceptible to activation of RAS in the heart and aorta, as a response to a fructose-rich diet (FRD).Materials and methods:Both male and female Wistar rats were given a 10% (w/v) fructose solution for 9 weeks. We measured the biochemical parameters, blood pressure (BP) and heart rate. We used Western blot and real-time polymerase chain reaction (PCR) to quantify protein and gene expression.Results:In the male rats, the FRD elevated BP and expression of cardiac angiotensin-converting enzyme (ACE), while the expression of angiotensin-converting enzyme 2 (ACE2) and angiotensin II Type 2 receptor (AT2R) were significantly decreased. In female rats, there were no changes in cardiac RAS expression due to FRD. Furthermore, the ACE/AT1R axis was overexpressed in the FRD male rats’ aortae, while only AT1R was upregulated in the FRD female rats’ aortae. ACE2 expression remained unchanged in the aortae of both genders receiving the FRD.Conclusions:The FRD induced gender-specific changes in the expression of the RAS in the heart and aortae of male rats. Further investigations are required in order to get a comprehensive understanding of the underlying mechanisms of gender-specific fructose-induced cardiovascular pathologies.

Sex differences in the metabolic effects of the renin-angiotensin system

“…Sex differences in expression, activity, and tissue responsiveness of several RAS components are apparent, with estrogen downregulating Ang II and upregulating Ang-(1-7) pathways [11]. In animal models of obesity, females appear to maintain circulating Ang-(1-7) levels [141] and are protected from hypertension and metabolic complications induced by angiotensinogen, renin, angiotensin II, and AT 1 R activation [38, 50, 142]. While inconsistent effects are observed in males, stimulation of counter-regulatory AT 2 R appears metabolically protective in female rodents [80, 114, 115, 147].…”

“…Furthermore, while females gain more weight and adiposity on HFD, only males exhibit increased circulating Ang II levels and AT 1 R-mediated hypertension [141]. Male fructose-fed rats develop elevations in blood pressure associated with increased cardiac AT 1 R and ACE gene expression, with females protected from these derangements [142]. In contrast, despite having lower blood pressure and reduced renal ACE, female rats are not protected from the vascular and renal damage in early-onset diabetes [143].…”

Involvement of the Renin‐Angiotensin System in Atherosclerosis

“…Genetic ACE2 deficiency underlines vascular inflammation and atherosclerosis in the ApoE-/-mice [111]. Protective role of ACE2 and AT2R in cardiovascular pathology is supported by their decreased expression in male rat hearts on fructose-rich diet [112].…”

Zoonotic evolution and implications of microbiome in viral transmission and infection

“…Obesity is also associated with dysbiosis and poor immune response against viral infections ( Alberca et al, 2020 ). A high-fat and fructose-rich diet which is mainly associated with obesity ( Namekawa et al, 2017 ), also reduces the ACE-2 levels significantly ( Bundalo et al, 2016 ). The consumption of higher amounts of processed food increases sodium intake which leads to higher oxidative stress and reduced ACE-2 expression in kidneys ( Bernardi et al, 2012 ), along with hypertension and CVD ( Hendriksen et al, 2014 ).…”