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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 fluorophenyl)-1H-pyrazol-4-yl)-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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The Newly Synthesized Pyrazole Derivative 5-(1-(3 Fluorophenyl)-1H-Pyrazol-4-yl)-2H-Tetrazole Reduces Blood Pressure of Spontaneously Hypertensive Rats via NO/cGMO Pathway