RESUMO
Chronic treatment with sildenafil (SILD) is an effective protector on the development of cardiovascular complications of pulmonary hypertension (PH) and diabetes. However, to date, no studies have evaluated the effect of SILD on cardiopulmonary pathophysiology during PH secondary to type 1 diabetes. AIM: The present study aimed to evaluate the beneficial effects of chronic SILD treatment on pulmonary arterial pressure, right ventricular hypertrophy (RVH) and cardiac autonomic dysfunction in rats with PH secondary to diabetes. METODOLOGY: Male Sprague Dawley rats were randomly distributed into the control group (saline), diabetic group (60 mg/kg with streptozotocin), SILD-treated control group (20 mg/kg) and SILD-treated diabetic group. RESULTS: After 8 weeks the type 1 diabetic animals presented PH, endothelial dysfunction of the pulmonary arteries, electrocardiographic alterations, RVH and overexpression of phosphodiesterase type 5 in the heart. In type 1 diabetic animals, SILD treatment prevented the development of PH, endothelial dysfunction and RVH. SILD treatment also prevented alterations in the corrected QT period and heart rate variability and prevented overexpression of phosphodiesterase type 5. CONCLUSION: Our results indicate for the first time that SILD treatment prevents pulmonary arterial endothelial dysfunction, pulmonary hypertension, right ventricular hypertrophy and improves heart rate variability in type 1 diabetic rats.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Hipertensão Pulmonar , Ratos , Masculino , Animais , Citrato de Sildenafila/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/prevenção & controle , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/prevenção & controle , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Frequência Cardíaca , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Diabetes Mellitus Tipo 1/complicações , Ratos Sprague-Dawley , Modelos Animais de DoençasRESUMO
Isorhamnetin and quercetin produced endothelium-independent vasodilator effects in rat aorta, rat mesenteric arteries, rat portal vein and porcine coronary arteries. The effects of the two flavonoids were similar in arteries stimulated by noradrenaline, KCl, U46619 or phorbol esters but the two flavonoids were more potent in the coronary arteries than in the aorta. At high concentrations, they also induced a positive inotropic effect in isolated rat atria. Therefore, at least part of the in vivo effects of quercetin may result from its conversion to isorhamnetin which is the main metabolite of quercetin found in plasma. The arterial, venous and coronary vasodilator effects may contribute to the protective effects of flavonoids in ischaemic heart disease observed in epidemiological studies.