Studies in humans have found consumption of certain flavanoid-containing foods to be associated with improvement in endothelial function and with reduction of blood pressure (BP). (-)-Epicatechin is a compound representative of the flavanols (a subfamily of flavonoids), abundant in cocoa seeds, which is preserved during the industrialization process to chocolate. The antihypertensive effect of dietary (-)-epicatechin was investigated on spontaneously hypertensive rats (SHRs). Consumption of (-)-epicatechin-supplemented diet (3 g (-)-epicatechin/kg diet) decreased BP in SHR by 27 and 23 mm Hg on days 2 and 6, respectively. On day 6, a 173% increase of nitric oxide synthase (NOS) activity was observed in the aorta of EPI-SHR as compared to nonsupplemented SHR (P < 0.05). Responses to acetylcholine (ACh) were then examined in femoral arteries in the absence and the presence of L-NAME, a nonselective NOS inhibitor, to assess the AChmediated relaxation ascribed to NO-dependent and -independent mechanisms. Acetylcholine-induced endothelium-dependent relaxation in the femoral artery was significantly higher in EPI-SHR than in SHR, with a predominance of the NO-dependent component of this relaxation. The endothelium-independent relaxation, assayed by using the NO donor sodium nitroprusside, resulted in nonsignificant difference in the three experimental groups, demonstrating an unaffected function of vascular smooth muscle cells. These results give further support to the concept that (-)-epicatechin can modulate BP in hypertension by increasing NO levels in the vasculature.V C 2013 IUBMB Life, 65(8):710-715, 2013

As chronic stress is a significant risk factor for several cardiovascular disorders, this study investigated the hypothesis that long-term stress produced by crowding may lead to alterations in nitric oxide (NO) production and NO-dependent relaxation in the course of stress, resulting in endothelial dysfunction and hypertension in Wistar-Kyoto (WKY) rats. For this purpose, male WKY rats were divided into control (480 cm2/rat, four rats/cage, n = 8) and crowded (200 cm2/rat, five rats/cage, n = 10) groups for 8 or 12 weeks. Vasorelaxation was evaluated in vitro as a response to acetylcholine (ACh) of femoral arteries pre-contracted by serotonin, before and after NO synthase inhibition (N (G)-nitro-l-arginine methyl ester, 300 μmol/l). Crowding increased plasma corticosterone concentration but failed to affect blood pressure (determined by tail-cuff plethysmography) of rats. NO production was unchanged in the hypothalamus and left ventricle of both stressed groups; however it was significantly elevated in the aorta. Maximal ACh-induced relaxation was elevated significantly after 8-week stress, but reduced after 12 weeks. Stress elevated the NO-dependent component and reduced the NO-independent component of ACh-induced relaxation in both crowded groups. However, a reduction in the NO-independent component was more pronounced after 12-week versus 8-week stress. In conclusion, elevated endothelium-dependent relaxation was observed after 8-week stress, while the extension of stress exposure resulted in a reduction in arterial relaxation associated with a more pronounced decrease of its NO-independent component. Thus, elevation of the NO-dependent component of relaxation can be considered as an adaptation mechanism, and impairment of NO-independent relaxation might be the initial step in chronic stress-induced cardiovascular disorders.

Information obtained from the arterial pulse waveform (APW) using haemodynamic parameters (HPs) is useful for characterization of the cardiovascular system in particular (patho)physiological conditions. Our goal was to find out whether the relationships between rat HPs could be described by simple mathematical functions and to find mathematical parameters for conditions of high blood pressure (BP) resulting from decreased NO bioavailability. The right jugular vein of anaesthetized Wistar rats was cannulated for I.V. administration of N -nitro-L-arginine methyl ester (L-NAME). The left common carotid artery was cannulated to detect the APW. From 10 points on the rat APW we defined 35 HPs (some were known already) and found 595 crossrelationships between HPs showing unique patterns for particular cardiovascular conditions.Here we show parallel time-dependent changes of 35 HPs and some of their cross-relationships in condition of high BP induced by L-NAME. We found that most of the time-dependent changes of 35 HPs and their relationships were very well fitted by simple mathematical functions, e.g. a linear function, exponential growth, exponential decay or exponential rise to maximum. The results may enable the mathematical functions to be assigned for decreased NO bioavailability, which may have predictive or diagnostic value for conditions of high BP.Using this approach, it may be possible to find unique cross-relationship patterns of HPs and mathematical functions between HPs for different cardiovascular (patho)physiological or drugmodulating conditions. This knowledge can be used in studying the molecular mechanisms of particular (patho)physiological conditions or drug actions and may have predictive or diagnostic value. K E Y W O R D Smathematical relationships, NO bioavailability, pulse waveform parameters INTRODUCTIONThe information obtained from an arterial pulse waveform (APW) analysis, as shape, amplitude and duration of the waveform, can provide insight into many diseases, including hypertension, coronary artery disease, diabetes and diastolic dysfunction (Nelson et al.,The APW gives useful information on details of the cardiovascular system, e.g. mechanical properties of the arterial tree, arterial stiffness, ventricular-vascular interaction and endothelial function. Several APW parameters have been introduced to characterize the cardiovascular system and the connection of pathological conditions with haemodynamic parameters, e.g. the augmentation index, dicrotic notch position, reflection time and cardiac output (Avolio, Butlin, & Walsh, 312 wileyonlinelibrary.com/journal/eph Experimental Physiology. 2020;105:312-334. 2 MATERIALS AND METHODS 2.1 Ethical approval All procedures were approved by the State Veterinary and Food Administration of the Slovak Republic (No: Ro-1545/15-221) according to the guidelines of Directive 2010/63/EU of the European Parliament. The procurement of animals, the husbandry and the experiments conform to the 'European Convention for the Protection