INFLUENCES OF CENTELLA ASIATICA AND CURCUMA LONGA ON ARTERIAL STIFFNESS IN A HYPERTENSIVE ANIMAL MODEL

There is a strong relationship between arterial stiffness and high blood pressure. Arterial stiffness increases the risk of a cardiovascular event and sudden death, especially in hypertensive patients. This study aimed to determine the effective combination of Centella asiatica and Curcuma longa on arterial stiffness in hypertensive animal models. Twenty-five male rats aged 2-3 months were randomly into five groups. The groups comprising the negative control and positive control group (receiving drug carriers), the test drug group receiving captopril 2.5 mg/kg, the combination of Centella asiatica (CA) and Curcuma longa (CL) doses of 50 and 100 mg/kg. Except for the control group, all groups received a high-fat diet and 25% fructose drinking water for 28 days. On day 15, they received test medicines. On days 0, 14, and 28, systolic and diastolic blood pressures, as well as the PWV (pulse wave velocity), were assessed. Nitric oxide levels in serum were measured using Griess reagents on day 28. The results showed that a combination of CA and CL doses of 50 and 100 mg/kg reduced systolic and diastolic blood pressure accompanied by a decrease in PWV and a statistically significant increase in serum NO levels (p <0.05). It concluded that a combination of CA and CL has the potential as antihypertensive, improving arterial elasticity.

Activation of Orexin 1 Receptors in the Paraventricular Nucleus Contributes to the Development of Deoxycorticosterone Acetate-Salt Hypertension Through Regulation of Vasopressin

Salt-sensitivity is a major factor in the development of hypertension. The brain orexin system has been observed to play a role in numerous hypertensive animal models. However, orexin’s role in the pathology of salt-sensitive hypertension (SSH) remains to be adequately explored. We assessed the impact of orexin hyperactivity in the pathogenesis of the deoxycorticosterone acetate (DOCA) – salt rat model, specifically through modulation of Arginine Vasopressin (AVP). Adult male rats were separated into three groups: vehicle control, DOCA-salt, and DOCA-salt+OX1R-shRNA. DOCA-salt rats received subcutaneous implantation of a 21-day release, 75 mg DOCA pellet in addition to saline drinking water (1% NaCl and 0.2% KCl). DOCA-salt+OX1R-shRNA rats received bilateral microinjection of AAV2-OX1R-shRNA into the paraventricular nucleus (PVN) to knockdown function of the Orexin 1-Receptor (OX1R) within that area. Following 2-week to allow full transgene expression, a DOCA pellet was administered in addition to saline drinking solution. Vehicle controls received sham DOCA implantation but were given normal water. During the 3-week DOCA-salt or sham treatment period, mean arterial pressure (MAP) and heart rate (HR) were monitored utilizing tail-cuff plethysmography. Following the 3-week period, rat brains were collected for either PCR mRNA analysis, as well as immunostaining. Plasma samples were collected and subjected to ELISA analysis. In line with our hypothesis, OX1R expression was elevated in the PVN of DOCA-salt treated rats when compared to controls. Furthermore, following chronic knockdown of OX1R, the hypertension development normally induced by DOCA-salt treatment was significantly diminished in the DOCA-salt+OX1R-shRNA group. A concurrent reduction in PVN OX1R and AVP mRNA was observed in concert with the reduced blood pressure following AAV2-OX1R-shRNA treatment. Similarly, plasma AVP concentrations appeared to be reduced in the DOCA-salt+OX1R-shRNA group when compared to DOCA-salt rats. These results indicate that orexin signaling, specifically through the OX1R in the PVN are critical for the onset and maintenance of hypertension in the DOCA-salt model. This relationship is mediated, at least in part, through orexin activation of AVP producing neurons, and the subsequent release of AVP into the periphery. Our results outline a promising mechanism underlying the development of SSH through interactions with the brain orexin system.

ATP-dependent chromatin remodeling complexes in embryonic vascular development and hypertension

Hypertension, a chronic elevation in blood pressure, is the largest single contributing factor to mortality worldwide and the most common preventable risk factor for cardiovascular disease. High blood pressure increases the risk for someone to experience a number of adverse cardiovascular events including heart failure, stroke, or aneurysm. Despite advancements in understanding factors that contribute to hypertension, the etiology remains elusive and there remains a critical need to develop innovative study approaches to develop more effective therapeutics. ATP-dependent chromatin remodelers are dynamic regulators of DNA-histone bonds and thus gene expression. The goal of this review is to highlight and summarize reports of ATP-dependent chromatin remodelers contribution to the development or maintenance of hypertension. Emerging evidence from hypertensive animal models suggests that induction of chromatin remodeler activity increases proinflammatory genes and increases blood pressure, whereas human studies demonstrate how chromatin remodelers may act as stress-response sensors to harmful physiological stimuli. Importantly, genomic studies have linked patients with hypertension to mutations in chromatin remodeler genes. Collectively, evidence linking chromatin remodelers and hypertension warrants additional research and ultimately could reveal novel therapeutic approaches for treating this complex and devastating disease.

Role of gut metabolism of adrenal corticosteroids and hypertension: clues gut-cleansing antibiotics give us

Intestinal bacteria can metabolize sterols, bile acids, steroid hormones, dietary proteins, fiber, foodstuffs, and short chain fatty acids. The metabolic products generated by some of these intestinal bacteria have been linked to a number of systemic diseases including obesity with Type 2 diabetes mellitus, some forms of inflammation, and more recently, systemic hypertension. In this review, we primarily focus on the potential role selected gut bacteria play in metabolizing the endogenous glucocorticoids corticosterone and cortisol. Those generated steroid metabolites, when reabsorbed in the intestine back into the circulation, produce biological effects most notably as inhibitors of 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2. Inhibition of the dehydrogenase actions of 11β-HSD, particularly in kidney and vascular tissue, allows both corticosterone and cortisol the ability to bind to and activate mineralocorticoid receptors with attended changes in sodium handling and vascular resistance leading to increases in blood pressure. In several animal models of hypertension, administration of gut-cleansing antibiotics results in transient resolution of hypertension and transfer of intestinal contents from a hypertensive animal to a normotensive animal produces hypertension in the recipient. Moreover, fecal samples from hypertensive humans transplanted into germ-free mice resulted in hypertension in the recipient mice. Thus, it appears that the intestinal microbiome may not just be an innocent bystander but certain perturbations in the type and number of bacteria may directly or indirectly affect hypertension and other diseases.