Journal
RESEARCH IN VETERINARY SCIENCE
Volume 130, Issue -, Pages 153-160Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.rvsc.2020.03.014
Keywords
Nitric oxide replacement therapy; Hypertension; Endothelial dysfunction; Ruthenium complex; Vasorelaxant effect
Categories
Funding
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (NRF Nascimento) [305759/2019-1]
- FUNCAP-MS-CNPq [PPSUS 03/2012]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (NRF Nascimento Universal) [438295/2018-8]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (LGF Lopes) [470054/2011-5, 303355/2018-2]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (EHS Sousa) [308383/2018-4]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (Universal) [403866/2016-2]
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The aim of this study was to investigate the antihypertensive properties of cis-[Ru(bpy)(2)ImN(NO)](3+) (FOR0811) in normotensive and in N-omega-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Vasorelaxant effects were analyzed by performing concentration response curve to FOR0811 in rat aortic rings in the absence or presence of 1H[1,2,4]-oxadiazolo- [4,3,-a] quinoxalin-1-one (ODQ), L-cysteine or hydroxocobalamin. Normotensive and L-NAME-hypertensive rats were treated with FOR0811 and the effects in blood pressure and heart rate variability in the frequency domain (HRV) were followed. FOR0811 induced relaxation in rat aortic rings. Neither endothelium removal nor L-cysteine altered the FOR0811 effects. However, the incubation with ODQ and hydroxocobalamin completely blunted FOR0811 effects. FOR0811 administered intravenously by bolus infusion (0.01-1 mg/bolus) or chronically by using subcutaneous implanted osmotic pumps significantly reduced the mean arterial blood pressure. The effect was long lasting and did not induce reflex tachycardia. FOR0811 prevented both LF and VLF increases in L-NAME hypertensive rats and has antihypertensive properties. This new ruthenium complex compound might be a promising nitric oxide donor to treat cardiovascular diseases.
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