Endoplasmic reticulum stress inhibition blunts the development of essential hypertension in the spontaneously hypertensive rat.

Essential hypertension is the leading cause of premature death worldwide. However, hypertension's cause remains uncertain. endoplasmic reticulum (ER) stress has recently been associated with hypertension, but it is unclear whether ER stress causes hypertension. To clarify this question, we examined if ER stress occurs in blood vessels before the development of hypertension and if ER stress inhibition would prevent hypertension development. We used the spontaneously hypertensive rat (SHR) as a model of human essential hypertension and the Wistar-Kyoto (WKY) rat as its normotensive control. Resistance arteries collected from young rats determined that ER stress was present in SHR vessels before the onset of hypertension. To assess the effect of ER stress inhibition on hypertension development, another subset of rats were treated with 4-phenylbutyric acid (4-PBA; 1 g·kg-1·day-1) for 8 wk from 5 wk of age. Blood pressure was measured via radiotelemetry and compared with untreated SHR and WKY rats. Mesenteric resistance arteries were collected and assessed for structural and functional changes associated with hypertension. Systolic and diastolic blood pressures were significantly lower in the 4-PBA-treated SHR groups than in untreated SHRs. Additionally, 4-PBA significantly decreased the media-to-lumen ratio and ER stress marker expression, improved vasodilatory response, and reduced contractile responses in resistance arteries from SHRs. Overall, ER stress inhibition blunted the development of hypertension in the SHR. These data add evidence to the hypothesis that a component of hypertension in the SHR is caused by ER stress. NEW & NOTEWORTHY In this study, 4-phenylbutyric acid's (4-PBA's) molecular chaperone capability was used to inhibit endoplasmic reticulum (ER) stress in the small arteries of young spontaneously hypertensive rats (SHRs) and reduce their hypertension. These effects are likely mediated through 4-PBA's effects to reduce resistant artery contractility and increase nitric oxide-mediated endothelial vasodilation through a process preventing endothelial dysfunction. Overall, ER stress inhibition blunted the development of hypertension in this young SHR model. This suggests that a component of the increase in blood pressure found in SHRs is due to ER stress. However, it is important to note that inhibition of ER stress was not able to fully restore the blood pressure to normal, suggesting that a component of hypertension may not be due to ER stress. This study points to the inhibition of ER stress as an important new physiological pathway to lower blood pressure, where other known approaches may not achieve blood pressure-lowering targets.

Guía de práctica clínica hipertensión arterial primaria o esencial en personas de 15 años y más / Clinical practice guideline for primary or essential arterial hypertension in people aged 15 years and over

Generar recomendaciones basadas en la mejor evidencia disponible acerca del manejo de personas con Hipertensión Arterial esencial en personas de 15 años y más. Personas con Hipertensión Arterial esencial en personas de 15 años y más que reciben atención en el nivel primario, secundario y terciario de salud en el sector público y privado de salud.

Nutrients and Nutraceuticals for the Management of High Normal Blood Pressure: An Evidence-Based Consensus Document.

Essential hypertension still represents the most common cardiovascular risk factor, which is responsible for the vast majority of global burden of disease, worldwide. Antihypertensive treatment aimed at lowering blood pressure (BP) levels to the recommended therapeutic targets has demonstrated to reduce risk of developing major cardiovascular, cerebrovascular and renal complications. Despite these evidence, overall rates of BP control are dramatically low in most European and Western countries, as well as in the so called developing countries, thus contributing to the increasingly amount of hypertension-related costs and disabilities. For these reasons, preventive strategies aimed at improving BP control rates in treated hypertensive patients and reducing high-normal BP levels in asymptomatic otherwise healthy individuals may contribute to reduce the burden of disease related to hypertension. In this view, an extensive use of nutrients and nutraceuticals has demonstrated to provide favorable effects in hypertension management and control, beyond the adoption of pharmacological and non-pharmacological interventions. These interventions can effectively and safely reduce BP levels to targets and prevent disease progression form high-normal BP levels towards stage 1 hypertension. The present consensus document will systematically describe and critically analyze the currently available evidence in favor of the use of nutrients and nutraceuticals in those individuals with high-normal BP levels at different cardiovascular risk profile.