According to the World Health Organization (WHO), an estimated 1.28 billion adults aged 30–79 years worldwide have hypertension; and every year, hypertension takes 7.6 million lives. High intakes of salt and sugar (mainly fructose from added sugars) have been linked to the etiology of hypertension, and this may be particularly true for countries undergoing the nutrition transition, such as Lebanon. Salt-induced hypertension and fructose-induced hypertension are manifested in different mechanisms, including Inflammation, aldosterone-mineralocorticoid receptor pathway, aldosterone independent mineralocorticoid receptor pathway, renin-angiotensin system (RAS), sympathetic nervous system (SNS) activity, and genetic mechanisms. This review describes the evolution of hypertension and cardiovascular diseases (CVDs) in Lebanon and aims to elucidate potential mechanisms where salt and fructose work together to induce hypertension. These mechanisms increase salt absorption, decrease salt excretion, induce endogenous fructose production, activate fructose-insulin-salt interaction, and trigger oxidative stress, thus leading to hypertension. The review also provides an up-to-date appraisal of current intake levels of salt and fructose in Lebanon and their main food contributors. It identifies ongoing salt and sugar intake reduction strategies in Lebanon while acknowledging the country’s limited scope of regulation and legislation. Finally, the review concludes with proposed public health strategies and suggestions for future research, which can reduce the intake levels of salt and fructose levels and contribute to curbing the CVD epidemic in the country.

We have previously shown that effector memory (TEM) cells accumulate in the bone marrow (BM) and the kidney in response to l-NAME/high salt challenge. It is not well understood if measures to block the exodus of that effector memory cells prevent redistribution of these cells and protect from hypertension-induced renal damage. We hypothesized that that effector memory cells that accumulate in the bone marrow respond to repeated salt challenges and can be reactivated and circulate to the kidney. Thus, to determine if mobilization of bone marrow that effector memory cells and secondary lymphoid organs contribute to the hypertensive response to delayed salt challenges, we employed fingolimod (FTY720), an S1PR1 functional antagonist by downregulating S1PR, which inhibits the egress of that effector memory cells used effectively in the treatment of multiple sclerosis and cardiovascular diseases. We exposed wild-type mice to the l-NAME for 2 weeks, followed by a wash-out period, a high salt diet feeding for 4 weeks, a wash-out period, and then a second high salt challenge with or without fingolimod. A striking finding is that that effector memory cell egress was dramatically attenuated from the bone marrow of mice treated with fingolimod with an associated reduction of renal that effector memory cells. Mice receiving fingolimod were protected from hypertension. We found that wild-type mice that received fingolimod during the second high salt challenge had a marked decrease in the renal damage markers. CD3+ T cell infiltration was significantly attenuated in the fingolimod-treated mice. To further examine the redistribution of bone marrow that effector memory cells in response to repeated hypertensive stimuli, we harvested the bone marrow from CD45.2 mice following the repeated high salt protocol with or without fingolimod; that effector memory cells were sorted and adoptively transferred (AT) to CD45.1 naïve recipients. Adoptively transferred that effector memory cells from mice treated with fingolimod failed to home to the bone marrow and traffic to the kidney in response to a high salt diet. We conclude that memory T cell mobilization contributes to the predisposition to hypertension and end-organ damage for prolonged periods following an initial episode of hypertension. Blocking the exodus of reactivated that effector memory cells from the bone marrow protects the kidney from hypertension-induced end-organ damage.

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Background and aims Adiponectin (APN), an adipocytokine, exerts cardioprotective effects, while angiotensin II (Ang II) plays a critical role in the pathogenesis of hypertrophy of vascular smooth muscle cells (VSMCs) induces hypertension and vascular remodeling. Ang II induces VSMC hypertrophy in part via activation of RhoA/ROCK pathway. In this study, we investigated the molecular mechanisms associated with Ang II‐induced RhoA activation and translocation and the ability of ANP to counteract Ang II‐hypertrophic effect through inhibition of RhoA activation, actin cytoskeleton remolding and reactive oxygen species (ROS) formation. Methods Studies were carried out using rat aortic tissues and VSMCs. The effect of APN on Ang II‐induced RhoA translocation was assessed by Western blotting (WB) and Immunohistochemistry. Leucine incorporation was used to examine NO effect on Ang II induced hypertrophy. The phosphorylation of cofilin‐2 and ERK1/2 was detected by WB. Moreover, immunohistochemistry was performed on aortic frozen sections to detect ROS, F‐actin and G‐actin levels, RhoA‐Cav 1 co‐localization and eNOS translocation. Results Ang II‐induced VSMCs hypertrophy was prevented by supplementing APN. The hypertrophic response to Ang II was associated with RhoA translocation to caveolae‐rich membrane, cofilin‐2 and ERK1/2 phosphorylation, in addition to a significant decrease in G/F actin ratio. Moreover, ROS production significantly increased with Ang II treatment as revealed by confocal microscopy. However, these effects were inhibited by APN and caveolae disruption. Taken together, these results suggest that Ang II hypertrophic effect is due, in part, to RhoA translocation to caveolae rich micro‐domains and its downstream effectors which is counteracted by APN. Conclusion These findings suggest the ability of APN to attenuate Angiotensin II‐induced vascular hypertrophy.

Hypertension is associated with an increase in reactive oxygen species (ROS). Cyclophilin A (CyPA) is released from vascular cells in response to oxidative stress and contributes to hypertension pathophysiology. Thereby, controlling redox imbalance and CyPA secretion may prevent hypertension-associated complications. Moreover, adiponectin (APN), an adipocyte-released cytokine, exerts protective effects on the cardiovascular system. Yet, the molecular mechanisms by which CyPA induces vascular remodeling and the role of APN in preventing CyPA secretion still need to be better understood. In this study, we used three models to mimic hypertension: The in-vivo rat portal vein (RPV) ligation and two ex-vivo models (The mechanically stretched RPVs and the angiotensin II treated rat aortas). Our results revealed plasma CyPA levels significantly increased after RPV ligation for 14 and 28 days. In addition, CyPA protein and mRNA expressions significantly increased in response to mechanical stretch and Ang-II. Furthermore, CyPA increased the wet weight of RPVs while inhibiting AMPK and eNOS phosphorylation/activation. Moreover, the CyPA effects on blood vessels were attenuated by pre-treatment with APN. In conclusion, CyPA is secreted in response to high blood pressure and promotes vascular hypertrophy by inhibiting AMPK and eNOS activities and activating the RhoA/ROCK pathway. On the other hand, APN attenuates the synthesis and release of CyPA induced by Ang-II and mechanical stretch.