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 Eyewear Case (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 Heart / Cardiovascular Support 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.