Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial

<p>Abstract</p> <p>Background</p> <p>Hawthorn extract has been used for cardiovascular diseases for centuries. Recent trials have demonstrated its efficacy for the treatment of heart failure, and the results of several small trials suggest it may lower blood pressure. However, there is little published evidence to guide its dosing. The blood pressure lowering effect of hawthorn has been linked to nitric oxide-mediated vasodilation. The aim of this study was to investigate the relationship between hawthorn extract dose and brachial artery flow mediated dilation (FMD), an indirect measure of nitric oxide release.</p> <p>Methods</p> <p>We used a four-period cross-over design to evaluate brachial artery FMD in response to placebo or hawthorn extract (standardized to 50 mg oligomeric procyanidin per 250 mg extract). Randomly sequenced doses of hawthorn extract (1000 mg, 1500 mg, and 2500 mg) and placebo were assigned to each participant. Doses were taken twice daily for 3 1/2 days followed by FMD and a 4-day washout before proceeding to the next dosing period.</p> <p>Results</p> <p>Twenty-one prehypertensive or mildly hypertensive adults completed the study. There was no evidence of a dose-response effect for our main outcome (FMD percent) or any of our secondary outcomes (absolute change in brachial artery diameter and blood pressure). Most participants indicated that if given evidence that hawthorn could lower their blood pressure, they would be likely to use it either in conjunction with or instead of lifestyle modification or anti-hypertensive medications.</p> <p>Conclusion</p> <p>We found no evidence of a dose-response effect of hawthorn extract on FMD. If hawthorn has a blood pressure lowering effect, it is likely to be mediated via an NO-independent mechanism.</p> <p>Trial Registration</p> <p>This trial has been registered with ClinicalTrials.gov, a service of the U.S. National Institutes of Health: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01331486">NCT01331486</a>.</p

Nanomechanics and Sodium Permeability of Endothelial Surface Layer Modulated by Hawthorn Extract WS 1442

The endothelial glycocalyx (eGC) plays a pivotal role in the physiology of the vasculature. By binding plasma proteins, the eGC forms the endothelial surface layer (ESL) which acts as an interface between bloodstream and endothelial cell surface. The functions of the eGC include mechanosensing of blood flow induced shear stress and thus flow dependent vasodilation. There are indications that levels of plasma sodium concentrations in the upper range of normal and beyond impair flow dependent regulation of blood pressure and may therefore increase the risk for hypertension. Substances, therefore, that prevent sodium induced endothelial dysfunction may be attractive for the treatment of cardiovascular disease. By means of combined atomic force - epifluorescence microscopy we studied the impact of the hawthorn (Crataegus spp.) extract WS 1442, a herbal therapeutic with unknown mechanism of action, on the mechanics of the ESL of ex vivo murine aortae. Furthermore, we measured the impact of WS 1442 on the sodium permeability of endothelial EA.hy 926 cell monolayer. The data show that (i) the ESL contributes by about 11% to the total endothelial barrier resistance for sodium and (ii) WS 1442 strengthens the ESL resistance for sodium up to about 45%. This mechanism may explain some of the vasoprotective actions of this herbal therapeutic

Erectile dysfunction and heart failure: the role of phosphodiesterase type 5 inhibitors

The phosphodiesterase type 5 (PDE-5) inhibitors are effective in treating erectile dysfunction (ED). ED and heart failure (HF) share similar risk factors, and commonly present together. This association has led to questions ranging from the safety and efficacy of PDE-5 inhibitors in HF patients to a possible role for this class of medication to treat HF patients with or without ED. In addition to endothelial dysfunction, there are causes of ED specific to patients with HF including low exercise tolerance, depression and HF medications. Before treating HF patients with PDE-5 inhibitors, patients should be assessed for their risk of a cardiac event during sexual activity. PDE-5 inhibitors are safe and effective in treating ED in HF patients. An improvement in erectile function by PDE-5 inhibitors was associated with an improvement in quality of life and reduction in depression. Several studies demonstrated the effect of PDE-5 inhibitors on HF per se. PDE-5 inhibitors improved endothelial dysfunction, increased exercise tolerance, decreased pulmonary vascular resistance and pulmonary artery pressure, and increased cardiac index. Several mechanisms whereby PDE-5 inhibitors improve HF have been proposed. PDE-5 inhibitors already have a role in treating primary pulmonary hypertension; however additional studies are needed to determine if they will become a standard therapy for HF patients

A review of the positive and negative effects of cardiovascular drugs on sexual function: a proposed table for use in clinical practice

Several antihypertensive drugs, such as diuretics and β-blockers, can negatively affect sexual function, leading to diminished quality of life and often to noncompliance with the therapy. Other drug classes, however, such as angiotensin II receptor blockers (ARBs) are able to improve patients’ sexual function. Sufficient knowledge about the effects of these widely used antihypertensive drugs will make it possible for cardiologists and general practitioners to spare and even improve patients’ sexual health by switching to different classes of cardiac medication. Nevertheless, previous data (part I) indicate that most cardiologists lack knowledge about the effects cardiovascular agents can have on sexual function and will thus not be able to provide the necessary holistic patient care with regard to prescribing these drugs. To be able to improve healthcare on this point, we aimed to provide a practical overview, for use by cardiologists as well as other healthcare professionals, dealing with sexual dysfunction in their clinical practices. Therefore, a systematic review of the literature was performed. The eight most widely used classes of antihypertensive drugs have been categorised in a clear table, marking whether they have a positive, negative or no effect on sexual function

The focal adhesion protein beta-parvin controls cardiomyocyte shape and sarcomere assembly in response to mechanical load

Physiological and pathological cardiac stress induced by exercise and hypertension, respectively, increase the hemodynamic load for the heart and trigger specific hypertrophic signals in cardiomyocytes leading to adaptive or maladaptive cardiac hypertrophy responses involving a mechanosensitive remodeling of the contractile cytoskeleton. Integrins sense load and have been implicated in cardiac hypertrophy, but how they discriminate between the two types of cardiac stress and translate mechanical loads into specific cytoskeletal signaling pathways is not clear Here, we report that the focal adhesion protein beta-parvin is highly expressed in cardiomyocytes and facilitates the formation of cell protrusions, the serial assembly of newly synthesized sarcomeres, and the hypertrophic growth of neonatal rat ventricular cardiomyocytes (NRVCs) in vitro. In addition, physiological mechanical loading of NRVCs by either the application of cyclic, uni-axial stretch, or culture on physiologically stiff substrates promotes NRVC elongation in a beta-parvin-dependent manner, which is achieved by binding of beta-parvin to alpha/beta-PIX, which in turn activates Rac1. Importantly, loss-of-function studies in mice also revealed that beta-parvin is essential for the exercise-induced cardiac hypertrophy response in vivo. Our results identify beta-parvin as a novel mechano-responsive signaling hub in hypertrophic cardiomyocytes that drives cell elongation in response to physiological mechanical loads