RESUMO
The literature review discusses the main pathological factors (hyperinsulinemia, hyperglycemia, insulin resistance, oxidative stress, neurohormonal activation, disturbances in the synthesis system, allocation and availability of nitric oxide, etc.) that underlie the development of endothelial dysfunction in diabetes mellitus and determine their role in the development and progression of vascular complications of this disease.
Assuntos
Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Humanos , Hiperglicemia/metabolismo , Hiperinsulinismo/metabolismo , Óxido Nítrico/metabolismo , Estresse OxidativoRESUMO
This review considers issues dealing with the role of nitric oxide and endothelial function/dysfunction in providing a number of physiological and pathophysiological processes and various body systems functioning. It also covers in details the possible ways of pharmacological management of endothelial dysfunction (ED) using drugs of different pharmacological groups (classes). Diverse pharmacological effects which have various degree of intensity and presented at various stages of ED pathogenesis are discussed. The value and urgency of search and development of agents with endothelial protection potential are studied in available experimental and clinical works on the considerable role of endothelial system in cardiovascular diseases and lack of specific means for prevention and treatment of endothelial dysfunction. Integrated morphological-functional approach to assessment of ED and endothelial protection of substances was developed and implemented in experimental practice in Cardiovascular Agents Laboratory of the Volgograd State Medical University Research Institute of Pharmacology. Various ED models were tested and most valid ones were selected. Endothelial protection of new compounds such as Salifen and Flavicin are considered and compared with cardiovascular drugs, antioxidants with metabolic effects, GABA derivatives. These drugs are assumed to belong to a new class of drugs--endothelial protection drugs.
Assuntos
Fármacos Cardiovasculares , Doenças Cardiovasculares/tratamento farmacológico , Endotélio Vascular , Substâncias Protetoras , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Desenho de Fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Flavonoides/farmacologia , Flavonoides/uso terapêutico , GABAérgicos/farmacologia , GABAérgicos/uso terapêutico , Humanos , Conduta do Tratamento Medicamentoso , Metabolismo , Óxido Nítrico/metabolismo , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêuticoRESUMO
Streptozotocin-induced diabetes leads to the development of endothelial dysfunction, as evidenced by decreased expression of endothelial nitric oxide synthase (eNOS) and increased expression of endothelin-1 as specific markers of endothelial disorders. All test substances showed endotelioprotective activity by increasing the concentration of eNOS and reducing the level of endothelin-1. With respect to the degree of impact on the eNOS and endothelin-1 levels, the compounds studied can be rated as follows: sulodexide > meksidol.
Assuntos
Endotelina-1/metabolismo , Endotélio/efeitos dos fármacos , Glicosaminoglicanos/farmacologia , Óxido Nítrico Sintase Tipo III/metabolismo , Picolinas/farmacologia , Animais , Biomarcadores/metabolismo , Glicemia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Endotelina-1/imunologia , Endotélio/metabolismo , Endotélio/fisiopatologia , Imuno-Histoquímica , Masculino , Óxido Nítrico Sintase Tipo III/imunologia , Ratos , Doenças Vasculares/metabolismoRESUMO
It is established that flavonoid flavicin improves antithrombotic and vasodilating functions of blood vessels in rats with endothelial dysfunction caused by streptozotocin-induced diabetes.