Exposure to a “safe” dose of environmental pollutant bisphenol A elevates oxidative stress and modulates vasoactive system in hypertensive rats

Abstract

Due to the prevalence of hypertension (one of the major risk factors of CVD) in the population, it is necessary to explore the adverse effects of daily tolerable and “safe” dose of bisphenol A (BPA) under hypertensive conditions. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME, 40 mg/kg b.w/day) induced hypertensive Wistar rats to BPA (50 μg/kg b.w/day) by oral administration along with appropriate controls for 30 days period. The results illustrate that a ‘safe’ dose of BPA does not influence the systolic blood pressure (SBP) and levels of circulatory biomarkers of tissue damage. On the other hand, BPA exposure significantly ( p < 0.05) elevates the thiobarbituric acid reactive substances (TBARS) content in plasma and tissues (heart, aorta, liver and kidney) in hypertensive rats when compared with respective control (BPA alone exposed) rats. Similarly, a significant modulation of ROS generation in RBC, plasma nitric oxide (NO) level and angiotensin-converting enzyme (ACE) activity was observed only under hypertensive milieu. In conclusion, the observed adverse effects during ‘safe’ dose of BPA exposure are specific to the hypertensive condition. Therefore, a precise investigation to explore the effects of BPA exposure in vulnerable hypertensive populations is highly suggested.

Exposure to low dose of Bisphenol A (BPA) intensifies kidney oxidative stress, inflammatory factors expression and modulates Angiotensin II signaling under hypertensive milieu

“…[ 74 ] Our previous study exposed the L‐NAME induced hypertensive Wistar rats to BPA (50 μg/kg b.w/day) and explored an elevated plasma ACE activity as a potentiation effect. [ 22 ] Similarly, the current observation in tissues also indicates that BPA exposure under hypertensive milieu potentiates the activity of tissue ACE under hypertensive milieu.…”

“…[21] At the physiological level, our previous study explored that low dose BPA does not influence blood pressure and renal markers under hypertensive settings. [22] However, beyond considering various compensatory mechanisms it is necessary to explore the impact at the tissue and cellular level to explain the hidden impacts on the renal system. Hence the current study aims to explore the adverse effect of low dose of BPA on renal tissue-associated enzymatic and molecular factors under a hypertensive milieu.…”

Bisphenol A (BPA) and Cardiovascular or Cardiometabolic Diseases

“…When post-weaned male mice were fed a low-protein diet for 8 weeks and then exposed to BPA (50 µg/kg/day) for the last 9 days, higher angiotensinogen mRNA expression was found in mice treated with a low-protein diet + BPA than in those fed a low-protein diet or BPA alone [220]. BPA treatment increased arterial AngII levels [225] and vascular smooth muscle cell proliferation through AngII-induced ERK1/2 activation [224] and stimulated the activation of the Angconverting enzyme under the hypertensive milieu [226]. Furthermore, BPA induces high blood pressure (hypertension) by reducing eNOS levels [205], increasing AngII/CaMKII-α uncoupling of eNOS [225], or enhancing vascular ROS/NO imbalance [228].…”

“…Angiotensin and blood pressure: BPA exposure increases the levels of angiotensin (Ang) [224,225], Ang-converting enzyme [226], and angiotensinogen (a precursor of Ang) [220], which play a critical role in cardiovascular physiology [227]. When post-weaned male mice were fed a low-protein diet for 8 weeks and then exposed to BPA (50 µg/kg/day) for the last 9 days, higher angiotensinogen mRNA expression was found in mice treated with a low-protein diet + BPA than in those fed a low-protein diet or BPA alone [220].…”