Vascular aging is associated with both structural and functional changes that can take place at the level of the endothelium, vascular smooth muscle cells and the extracellular matrix of blood vessels. With regard to the endothelium, reduced vasodilatation in response to agonists occurs in large conduit arteries as well as in resistance arteries with aging. Reviews concerning the different hypotheses that may account for this endothelial dysfunction have pointed out alterations in the equilibrium between endothelium-derived relaxing and constricting factors. Thus, a decreased vasorelaxation due to nitric oxide and, in some arteries, endothelium-derived hyperpolarizing factor as well as an increased vasoconstriction mediated by cyclooxygenase products such as thromboxane A2 are likely to occur in age-induced impairment of endothelial vasodilatation. Furthermore, enhanced oxidative stress plays a critical role in the deleterious effect of aging on the endothelium by means of nitric oxide breakdown due to reactive oxygen species. The relative contribution of the above phenomenon in age-related endothelial dysfunction is highly dependent on the species and type of vascular bed., R. L. Matz, C. Schott, J. C. Stoclet, R. Andriantsitohaina., and Obsahuje bibliografii
The aim of the present study was to investigate the endothelial function in human mesenteric arteries with specific reference to defining the role of endothelium-derived nitric oxide (EDNO) and the endothelium-derived hyperpolarizing factor (EDHF). Isolated segments of small human mesenteric arteries (225-450 μm inner diameter) were mounted in organ baths for recording isometric tension. In arteries precontracted with U46619 (thromboxane A2 analogue, 10-7 M), endothelium-dependent relaxations were induced in a concentration-dependent manner by substance P and histamine. In normal Krebs solution the relaxations to substance P (10-9 M) and histamine (10-7 M) were not significantly affected by preincubation with Nω-nitro-L-arginine (L-NNA, 10-4 M) or indomethacin (10-5 M). When the preparations were exposed to a solution containing 60 mM KCl, stable contractions were induced, but relaxations could still be induced by substance P and histamine. When the arteries were further preincubated with L-NNA, the relaxations were almost abolished. A combination of apamin (3 x 10-7 M) and charybdotoxin (10-9 M) almost abolished relaxations in normal Krebs solution. It is concluded that isolated human mesenteric arteries respond to substance P and histamine with relaxations that are endothelium-dependent. Synthesis of both EDNO and EDHF seem important for these relaxations, whereas prostaglandins seem to be of minor importance.
This study investigated the effect of exercise training on the flow- mediated dilation (FMD) in gastrocnemius muscle arteries from spontaneously hypertensive rats (SHR). SHR and WKY rats were divided into sedentary and exercised groups. After swimming exercise for eight weeks, the isolated arteries were mounted on pressurized myograph and FMD re sponses examined. The role of nitric oxide (NO), prostaglandins (PGs) and endothelium derived hyperpolarizing factor (EDHF) on FMD were assessed by obtaining dilation responses in the presence and absence of pharmacological antagonists. Nω-nitro-L-arginine methyl ester (L-NAME), indomethacin (INDO) and tetraethylamonium (TEA) were used to inhibit nitric oxide synthase, cyclooxygenase and EDHF-mediated responses, respectively. The FMD response was significantly blunted in arteries of SHR compared with WKY rats, and, improved by exercise training in SHR (SHR-ET) group. In SHR arteries, L-NAME and TEA did not affect dilation responses to flow, while INDO led to a significant enhancement in this response. Although dilation response was not altered by L-NAME in arteries obtained from trained SHR, TEA caused a significant attenuation and INDO led to significant increases. These results demonstrate that exercise training improves FMD in SHR, and, this enhancement induced by exercise training occurs through EDHF-mediated mechanism(s)., F. Gündüz ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to determine the relative contribution of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in histamine-induced relaxation of isolated pulmonary artery from normotensive and hypertensive rats. The hypertension was induced by oral administration of NO synthase inhibitor NG-nitro-L-arginine methylester (L-NAME, 50 mg/kg/day) to normotensive rats for 8 weeks. In phenylephrine-precontracted arterial rings the histamine-induced relaxation was significantly reduced in L-NAME-treated rats compared to the controls. Indomethacin (cyclooxygenase inhibitor) and glibenclamide (ATP-sensitive K+-channel blocker) did not inhibit the relaxation response in either control or hypertensive rats. On the other hand, tetraethylammonium (TEA), a K+-channel blocker with a broad specificity, significantly reduced histamine-induced relaxation in the pulmonary artery from both groups examined. The TEA-resistant relaxation was completely abolished by additional administration of L-NAME to the incubation medium. The results indicate that histamine-induced relaxation of the pulmonary artery in both normotensive and hypertensive rats is mediated mainly by nitric oxide, whereas EDHF seems to play a minor role., J. Török., and Obsahuje bibliografii