Vascular remodelling is an adaptive mechanism, which counteracts pressure changes in blood circulation. Nicotine content in cigarette increases the risk of hypertension. The exact relationship between nicotine and vascular remodelling still remain unknown. Current study was aimed to determine the effect of clinically relevant dosage of nicotine (equivalent to light smoker) on aortic reactivity, oxidative stress markers and histomorphological changes. Twelve age-matched male Sprague-Dawley rats were randomly divided into two groups, i.e.: normal saline as control or 0.6 mg/kg nicotine for 28 days (i.p., n=6 per group). On day-29, the rats were sacrificed and the thoracic aorta was dissected immediately for further studies. Mean arterial pressure (MAP) and pulse pressure (PP) of nicotine-treated vs. control were significantly increased (p<0.05). Nicotine-treated group showed significant (p<0.05) increase tunica media thickness, and decrease in lumen diameter, suggesting vascular remodelling which lead to prior hypertension state. The phenylephrine (PE)-induced contractile response in nicotine group was significantly higher than control group (ED50=1.44×105 M vs. 4.9×106 M) (p<0.05~0.001). However, nicotine-treated rat showed significantly lower endothelium-dependent relaxation response to acetylcholine (ACh) than in control group (ED50=6.17×107 M vs. 2.82×107 M) (p<0.05), indicating loss of primary vascular function. Malondialdehyde (MDA), a lipid peroxidation marker was significantly higher in nicotine group. Superoxide dismutase (SOD) enzymatic activity and glutathione (GSH) were all reduced in nicotine group (p<0.05) vs. control, suggesting nicotine induces oxidative imbalance. In short, chronic nicotine administration impaired aortic reactivity, probably via redox imbalance and vascular remodelling mechanism.

Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt , suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.

Nox5 is a unique Ca 2+-sensitive Nox isoform that is expressed in human vascular smooth muscle cells (VSMC). Although Nox5 has been implicated in diabetic nephropathy, its role in vascular function and development of hypertension remain unclear. Nox5 is not expressed in rodents, and accordingly we generated humanised Nox5 mice with Nox5 expressed in a VSMC-specific manner (Nox5SM22). Control (wild-type) and Nox5SM22 mice were infused with Ang II (600 ng/Kg/day). Blood pressure (BP) was assessed by tail-cuff. Vascular function and structure of resistance arteries were measured by myography. Ang II increased BP in WT and Nox5SM22 mice with no significant differences. Arteries from Nox5SM22 mice exhibited reduced endothelium-dependent relaxation versus WT controls (%ACh relaxation: 55.1±4 vs ctl: 81.6±7%). Fasudil (Rho kinase inhibitor)-induced relaxation was reduced in Nox5SM22 mice versus controls (%Fas relaxation: 111.3±11 vs ctl: 166.6±8%) (p<0.05). Ang II increased the maximal contraction to U46619 (thromboxane A2 mimetic) in WT (115.8±2 vs untreated: 101.4±2%) and Nox5SM22 (121.3±3 vs untreated: 99.1±2) (p<0.05) and induced endothelial dysfunction in all groups. Fasudil-induced relaxation was impaired by Ang II in WT (102.7±6 vs untreated: 166.6±8%, p<0.05) but not further impaired in Nox5SM22 mice (114.9±6 vs untreated: 111.3±11%). Ang II increased cross-sectional area (CSA) and lumen diameter) while in Nox5SM22 mice, Ang II increased wall thickness, wall-to-lumen ratio, CSA and decreased lumen diameter, with associated increased vascular stiffness. Our findings indicate that in mice expressing human Nox5 in VSMCs, endothelium-dependent relaxation is impaired, fasudil-mediated vasodilation is attenuated and vessels undergo exaggerated hypertrophic inward remodelling with increased stiffness; processes that occur independently of BP elevation. These data suggest an important role for Nox5 in Ang II-induced vascular dysfunction and remodelling, but not in the development of hypertension. Moreover, we identify Rho kinase as a putative target for Nox5-induced vascular injury. We provide novel insights into Nox5 vascular biology and demonstrate that vascular Nox5 actions are dissociated from BP effects. Introduction Thoracic aortic aneurysms (TAA) are common in patients with bicuspid aortic valve (BAV). ADAMTS-1 (a disin-tegrin and metalloproteinase with thrombospondin motifs) has recently been implicated in TAA formation (Oller et al, Nat Med, 2017). The contribution of other ADAMTS proteases to TAA is currently unknown. Method Using proteomics, we compared the extracellular matrix (ECM) composition in the greater (i.e. the aneurysm-prone area) and lesser curvatures of TAA in BAV patients. Our findings in patients were complemented by studies in ADAMTS-5 deficient mice. Results In BAV patients with TAA, the large aggregating pro-teoglycan versican was the most differentially regulated ECM protein in the aneurysm-prone area. In mice, ADAMTS-5 is the main versican-degrading member of the ADAMTS family. Hence, a mo...

Hypertension can be caused by various factors while the predominant causes include increase in body fluid volume and resistance in the circulatory system that elevate the blood pressure. Consumption of probiotics has been proven to attenuate hypertension; however, the effect is much strain-dependent. In this study, a newly isolated Lactobacillus casei (Lb. casei) strain C1 was investigated for its antihypertensive properties in spontaneously hypertensive rats (SHR). Lactic acid bacteria (LAB) suspension of 11 log colony-forming unit (CFU) was given to SHR (SHR+LAB, n=8), and phosphate buffer saline (PBS) was given as a control in SHR (SHR, n=8) and in Wistar rats as sham (WIS, n=8). The treatment was given via oral gavage for 8 weeks. The results showed that the weekly systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and aortic reactivity function were remarkably improved after 8 weeks of bacterial administration in SHR+LAB. These effects were mostly attributed by restoration of wall tension and tensile stress following the bacterial treatment. Although not statistically significant, the level of malondialdehye (MDA) in SHR+LAB serum was found declining. Increased levels of glutathione (GSH) and nitric oxide (NO) in SHR+LAB serum suggested that the bacterium exerted vascular protection through antioxidative functions and relatively high NO level that induced vasodilation. Collectively, Lb. casei strain C1 is a promising alternative for hypertension improvement.

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