Journal
FRONTIERS IN PHYSIOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2018.01073
Keywords
spontaneously hypertensive rats; pyrazole derivative; antihypertensive drugs; vasodilatation; muscarinic receptors
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Funding
- Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG) [2012/0055431086, 2009/10267000352]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [477832/2010-5, 483411/2012-4, 447496/2014-0]
- Incubadora 3D (Aparecida de Goiania - GO)
- Fundacao de Desenvolvimento de Tecnopolis (Funtec) [001/2016]
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The search for new antihypertensive drugs has grown in recent years because of high rate of morbidity among hypertensive patients and several side effects that are associated with the first-line medications. The current study sought to investigate the antihypertensive effect of a newly synthesized pyrazole derivative known as 5-(1-(3 fluoropheny1)-1H-pyrazol-4-y1)-2H-tetrazole (LQFM-21). Spontaneously hypertensive rats (SHR) were used to evaluate the effect of LQFM-21 on mean arterial pressure (MAP), heart rate (HR), renal vascular conductance (RVC), arterial vascular conductance (AVC), baroreflex sensitivity (BRS) index, and vascular reactivity. Acute intravenous (iv) administration of LQFM-21 (0.05, 0.1, 0.2, and 0.4 mg kg(-1)) reduced MAP and HR, and increased RVC and AVC. Chronic oral administration of LQFM-21 (15 mg kg(-1)) for 15 days reduced MAP without altering BRS. The blockade of muscarinic receptors and nitric oxide synthase by intravenous infusion of atropine and L-NAME, respectively, attenuated cardiovascular effects of LQFM-21. In addition, ex vivo experiments showed that LQFM-21 induced an endothelium-dependent relaxation in isolated aortic rings from SHR. This effect was blocked by guanylyl cyclase inhibitor (ODQ) and L-NAME. These findings suggest the involvement of muscarinic receptor and NO/cGMP pathway in the antihypertensive and vasodilator effects of LQFM-21.
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