Sodium nitrite improves hypertension-induced myocardial dysfunction by mechanisms involving cardiac S-nitrosylation
| Autor: | Rose I.M. Batista, Rafael L. Portella, Renato C. Nogueira, Lucas C. Pinheiro, Evandro M. Neto-Neves, Jose E. Tanus-Santos |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Cardiac function curve medicine.medical_specialty Nitrosation Blood Pressure 030204 cardiovascular system & hematology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Plethysmograph Rats Wistar Nitrite Sodium nitrite Molecular Biology Antihypertensive Agents NITRITOS Nitrates Sodium Nitrite biology business.industry Myocardium Starling Snap Heart S-Nitrosylation biology.organism_classification Rats Oxidative Stress 030104 developmental biology Blood pressure chemistry Hypertension Cardiology Cardiomyopathies Cardiology and Cardiovascular Medicine business |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 0022-2828 |
| DOI: | 10.1016/j.yjmcc.2019.06.012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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