Small conductance calcium-activated potassium channels and nitric oxide/cGMP pathway mediate cardioprotective effects of Croton urucurana Baill. In hypertensive rats.
Autor: | Lopes KS; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil., Marques AAM; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil., Moreno KGT; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil., Lorençone BR; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil., Leite PRT; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil., da Silva GP; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil., Dos Santos AC; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil., Souza RIC; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil., Gasparotto FM; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil., Cassemiro NS; Laboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil., Lourenço ELB; Laboratory of Preclinical Research of Natural Products, Paranaense University, Umuarama, PR, Brazil., Klider LM; Laboratory of Reproductive Toxicology, Department of Pharmacology, Federal University of Parana, Curitiba, PR, Brazil; Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa, Brazil., Manfron J; Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa, Brazil., Silva DB; Laboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil., Gasparotto Junior A; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil. Electronic address: arquimedesjunior@ufgd.edu.br. |
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Jazyk: | angličtina |
Zdroj: | Journal of ethnopharmacology [J Ethnopharmacol] 2022 Jul 15; Vol. 293, pp. 115255. Date of Electronic Publication: 2022 Apr 07. |
DOI: | 10.1016/j.jep.2022.115255 |
Abstrakt: | Ethnopharmacological Relevance: Croton urucurana Baill. (Euphorbiaceae), popularly known as 'sangue de dragão' is a Brazilian species widely used in traditional medicine for cardiovascular ailments. Aim: To investigate the cardiovascular effects of the C. urucurana extract in spontaneously hypertensive rats (SHRs). Materials and Methods: Leaves from C. urucurana were collected and morphoanatomically characterized. The ethanol-soluble fraction (ESCU) was obtained and analyzed by LC-DAD-MS. Using female Wistar rats we investigated the acute toxicity of ESCU. Then, SHRs (six months old) received vehicle, hydrochlorothiazide (25 mg/kg), or ESCU (30, 100, 300 mg/kg) for 28 days. At the beginning and at the end of treatments, urine samples were obtained to assess renal function. At the end of the trial period, the blood pressure, mesenteric vascular beds (MVBs) reactivity, and electrocardiographic profile were evaluated. Serum angiotensin-converting enzyme activity, as well as urea, creatinine, sodium, potassium, nitrite, malondialdehyde, nitrotyrosine, and aldosterone levels were determined. Relative organ weights and histopathological analysis were performed. Finally, the cardiac function on a Langendorff system, as well as the molecular mechanisms involved in the vasodilator effects of ESCU in MVBs were also investigated. Results: The compounds annotated from ESCU by LC-DAD-MS included mainly phenylpropanoid derivatives, alkaloids, O-glycosylated megastigmanes, glycosylated flavonoids, flavan-3-ols, and others, such as quercetin O-deoxyhexosyl-hexoside, magnoflorine, reticuline, and taspine. None of the animals showed any signs of toxicity. Male SHRs treated only with the vehicle showed important cardiovascular changes, including a reduction in renal function, increase in serum oxidative stress, and hemodynamic, electrocardiographic, and morphological changes typical of hypertensive disease. Moreover, parameters of cardiac function, including left ventricular developed pressure, peak rate of contraction, peak rate of relaxation, and the rate pressure product were significantly altered, showing a significant impairment of ventricular function. All ESCU-doses presented a significant cardioprotective effect in SHRs rats. The 28-day treatment normalized the hemodynamic, electrocardiographic, morphological, and renal impairments, as well as reversed the changes in ventricular function induced by hypertension. In MVBs with an intact endothelium, ESCU (0.1, 0.3, and 1 mg) dose-dependently induced vasodilation. Endothelium removal or the inhibition of nitric oxide synthase prevented the vasodilatory effect of ESCU. Perfusion with a physiological saline solution that contained KCl, tetraethylammonium, or apamin also abolished the vasodilatory effect of ESCU. Conclusion: Prolonged ESCU-treatment showed significant cardioprotective effects in SHRs. Moreover, the data showed the role of nitric oxide and calcium-activated small conductance potassium channels in the cardiovascular effects of ESCU. (Copyright © 2022 Elsevier B.V. All rights reserved.) |
Databáze: | MEDLINE |
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