sodium-nitrite and Cardiomyopathies

Although nitrite improves vascular function and lowers blood pressure, its cardiac effects are not completely known. We investigated whether nitrite improves the cardiac function in normotensive and in hypertensive rats. Two-kidney, one-clip hypertension model (2K1C) was induced in Wistar rats. Blood pressure was evaluated by tail-cuff plethysmography over 6 weeks. By the end of week 2, hypertensive and normotensive rats received nitrite (daily dose of 1 or 15 mg/kg) by gavage for 4 weeks. Cardiac morphology and function were performed by transthoracic echocardiography. Intrinsic heart function was evaluated using the isolated heart model (Langendorff's preparation). Starling curves were generated under nitrite (1 μmol/L) and/or ascorbate (1 mmol/L) or vehicle. Cardiac tissue was collected and snap frozen for biochemical analysis. Nitrite treatment (15 mg/kg) lowered both systolic blood pressure and the increases in left ventricular (LV) mass found in 2K1C rats (P < .05). In addition, nitrite treatment restored the decreased cardiac output in 2K1C rats (P < .05) and improved the cardiac function. These findings were associated with increased nitrite, S-nitrosothiols, and protein S-nitrosylation (all P < .05) assessed in heart tissue. The cardiac effects of nitrite were further investigated in the isolated heart model, and nitrite infusion (1 μmol/L) enhanced cardiac contractility and relaxation. This infusion increased S-nitrosothiols concentrations and protein S-nitrosylation in the heart. Ascorbate completely blunted all nitrite-induced effects. These findings show that treatment with oral nitrite improves cardiac function by mechanisms involving increased S-nitrosothiols generation and S-nitrosylation of cardiac proteins. Pharmacological strategies promoting cardiac S-nitrosylation may be useful to improve myocardial function in heart diseases.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Cardiomyopathies; Heart; Hypertension; Male; Myocardium; Nitrates; Nitrosation; Oxidative Stress; Rats; Rats, Wistar; Sodium Nitrite

Under the condition of acute NaNO2 poisoning, the changes of myocardial GSH-Px activity of rats fed a diet composed of grains grown in the endemic region of Keshan disease and the same diet with supplementation of vitamin E or selenium were investigated. By gavage of toxic doses of NaNO2, the myocardial GSH-Px was significantly reduced (P less than 0.05). Vitamin E or selenium supplementation protected the enzyme activity from reducing. It is suggested that the simultaneous action of an increase in selenium and vitamin E intake and a decrease in nitrite intake might greatly prevent the occurrence of Keshan disease.

Topics: Animals; Cardiomyopathies; Glutathione Peroxidase; Myocardium; Rats; Selenium; Sodium Nitrite; Vitamin E

Quinacrine hydrochloride is toxic for the heart of F-344 rats. Rats treated with 500 ppm quinacrine hydrochloride in the diet all developed a high incidence of left atrial thrombosis. The lesion was associated with cardiac hypertrophy and dilatation and focal myocardial degeneration. Rats died from cardiac hypertrophy with severe acute and chronic congestion of the lungs, liver, and other organs. Seventy percent of rats given 250 ppm quinacrine hydrochloride and 1,000 ppm sodium nitrite simultaneously in the diet had thrombosis of the atria of the heart, while untreated control rats in this laboratory did not have atrial thrombosis. Sodium nitrite in combination with quinacrine hydrochloride appeared to have no additional effect.

Topics: Animals; Cardiomyopathies; Chemical and Drug Induced Liver Injury; Female; Heart Atria; Heart Diseases; Lung Diseases; Male; Quinacrine; Rats; Rats, Inbred F344; Sex Factors; Sodium Nitrite; Thrombosis; Time Factors