RESUMO
In many developed countries the prevalence of venous disorders and its consequences are higher than that of arterial diseases. Thus it is very important to understand the exact physiological and pathophysiological function of small veins and their control mechanisms. Small veins and venules have an important role in the regulation of capillary fluid exchange, as well as return of the venous blood into the heart. However, there is only limited knowledge available regarding the role of local mechanisms controlling the vasomotor tone and diameter of small veins. In the last decade the authors focused on the elucidation of these mechanisms in isolated skeletal muscle venules of rats. Their results suggest that the tone of small veins is controlled by the integration of several mechanisms, activated by the intraluminal pressure and flow/wall shear stress, in addition to numerous local mediators synthesized and released from the smooth muscle and endothelium. These mechanisms are involved - in a complex manner - in the control of postcapillary resistance, thus regulation of tissue blood supply, venous return and consequently in the modulation of the cardiac output, as well.
Assuntos
Pressão Sanguínea , Hemorreologia , Músculo Esquelético/irrigação sanguínea , Sistema Vasomotor/fisiologia , Vênulas/fisiologia , Acetilcolina/fisiologia , Animais , Endotélio Vascular/fisiologia , Humanos , Peróxido de Hidrogênio/metabolismo , Microcirculação/fisiologia , Óxido Nítrico Sintase/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Vênulas/inervaçãoRESUMO
INTRODUCTION: We tested the hypothesis that asymmetric dimethylarginine (ADMA) interferes with other mechanisms in addition to inhibition of nitric oxide synthase (NOS). Thus, in skeletal muscle arterioles, in the presence of ADMA, we investigated the dilator effect of an NO donor and increases in flow and aimed to elucidate the underlying mechanisms, including the role of oxidative stress, which is known to reduce the bioavailability of NO. METHODS AND RESULTS: In isolated rat gracilis skeletal muscle arterioles (â¼160 µm at 80 mm Hg), ADMA (similarly to pyrogallol) reduced dilations to sodium nitroprusside (SNP), which was significantly prevented by the presence of superoxide dismutase (SOD) and catalase (CAT): SNP 10(-8)M; control: 43.2 ± 3%, ADMA: 4.9 ± 1%, ADMA + SOD/CAT: 30.2 ± 9% (p < 0.05). Also, ADMA reduced basal diameter and flow-induced dilations, which were not restored by L-arginine, but prevented by SOD/CAT and by inhibition of NAD(P)H oxidase (but not xanthine oxidase) and by an angiotensin-converting enzyme inhibitor or an angiotensin type 1 receptor blocker (ARB). ADMA increased the production of reactive oxygen species detected by lucigenin-enhanced chemiluminescence, which was significantly inhibited by SNP or ARB. CONCLUSION: We suggest that by activating the vascular renin-angiotensin-NAD(P)H oxidase pathway, ADMA elicits oxidative stress, which interferes with the bioavailability of NO and consequently reduces NO-mediated dilations.
Assuntos
Arginina/análogos & derivados , Doadores de Óxido Nítrico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Acetofenonas/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Arginina/farmacologia , Arteríolas/efeitos dos fármacos , Catalase/metabolismo , Masculino , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , NADPH Oxidases/antagonistas & inibidores , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroprussiato/farmacologia , Estresse Oxidativo , Pirogalol/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Xantina Oxidase/metabolismoRESUMO
Although ischemia-reperfusion (I/R) strongly influences muscle flap survival in reconstructive surgery, there is limited knowledge about its relation to hemorheological parameters and oxidative stress markers in flaps. In the present study we investigated these changes during I/R of latissimus dorsi muscle (LDM) flaps in beagle dogs. In four animals LDM flaps were prepared bilaterally. The right side served as control, while the left side's vascular pedicle was clamped for 60 minutes, and a 60-minute reperfusion was allowed afterward. Blood samples (0.5 ml each) were taken from the pedicle's vein bilaterally before and after the ischemia, and at the 5th, 15th, 30th, 45th, and 60th minutes of the reperfusion, for hematological and erythrocyte aggregation tests. In muscle biopsies, taken before and after I/R, histological investigations and tests for measuring gluthation-peroxidase (GSH-PX) activity, glutathione (GSH) and carbonyl concentrations, and thiobarbituric acid reactive substances (TBARS) content were carried out. In I/R side leukocyte count increased during the reperfusion with a peak at the 30th minute. Hematocrit continuously increased from the 15th minute. In the first 5 minutes of the reperfusion, erythrocyte aggregation increased, than tented to be normalized. In muscle homogenates GSH-PX activity did not change markedly, GSH content slightly decreased, carbonyl and TBARS content increased during reperfusion. A 1-hour ischemia and reperfusion of LDM flaps caused local changes of leukocyte distribution and erythrocyte aggregation, supposedly due to the metabolic and inflammatory reactions. Oxidative damage during reperfusion was also demonstrated.