The NO-cGMP-K+ Channel Pathway Participates in Diuretic and Cardioprotective Effects of Blutaparon portulacoides in Spontaneously Hypertensive Rats

Author:

Terço Leite Patrícia Regina1,Lorençone Bethânia Rosa1,Moreno Karyne Garcia Tafarelo1,Lopes Katiana Simões1,Marques Aline Aparecida Macedo1,Fortini Clara Soligo1,Palozi Rhanany Alan Calloi1,Dalmagro Mariana2,Kassuya Cândida Aparecida Leite3,dos Santos Ariany Carvalho4,Salvador Marcos José5,Gasparotto Junior Arquimedes1ORCID

Affiliation:

1. Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil

2. Postgraduate Program in Biotechnology Applied to Agriculture, Paranaense University, Umuarama, Paraná, Brazil

3. Laboratory of Immunoinflammation and Cell Culture, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil

4. Laboratory of Histology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil

5. Institute of Biology, Department of Plant Biology, University of Campinas, Campinas, São Paulo, Brazil

Abstract

Abstract Blutaparon portulacoides is a Brazilian plant species that is widely used in folk medicine. The present study investigated the role of an aqueous extract of B. portulacoides against hypertension in spontaneously hypertensive rats. The aqueous extract of B. portulacoides was obtained from the whole plant. Its chemical profile was analyzed by ultraperformance liquid chromatography-tandem mass spectrometry. The acute toxicity of the aqueous extract of B. portulacoides was evaluated in female Wistar rats. Male 6-month-old spontaneously hypertensive rats then received the aqueous extract of B. portulacoides (30, 100, and 300 mg/kg), hydrochlorothiazide (25 mg/kg), or vehicle once daily for 28 days. On days 1, 14, and 28, the diuretic effects of the aqueous extract of B. portulacoides were evaluated. The role of prostaglandins and the nitric oxide-cyclic guanosine monophosphate-potassium channel pathway in the diuretic activity of the aqueous extract of B. portulacoides was also investigated. At the end of the treatment, hepatic and renal biochemical markers, serum nitrotyrosine, malondialdehyde, nitrite, and aldosterone levels, and angiotensin-converting enzyme activity were measured. The electrocardiographic profile, blood pressure, and renal vascular reactivity were also assessed. The heart, kidneys, and liver were collected to determine relative organ weight, histopathology, and cardiac morphometry. Caffeic acid, ferulic acid, and several flavonoids were identified in the aqueous extract of B. portulacoides. No signs of toxicity were observed. Prolonged treatment with the aqueous extract of B. portulacoides (300 mg/kg) induced significant diuretic activity by activating the nitric oxide-cyclic guanosine monophosphate-potassium channel pathway. These effects reduced blood pressure and oxidative stress and prevented renal vascular dysfunction and left ventricular hypertrophy that was induced by hypertension. Overall, the present data suggest that the aqueous extract of B. portulacoides has important diuretic and cardioprotective effects by activation of the nitric oxide-cyclic guanosine monophosphate-potassium channel pathway.

Funder

Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Georg Thieme Verlag KG

Subject

Organic Chemistry,Complementary and alternative medicine,Drug Discovery,Pharmaceutical Science,Pharmacology,Molecular Medicine,Analytical Chemistry

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