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

Abstract

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.

Photochemistry of 1-Phenyl-4-Allyl-Tetrazol-5-One: A Theoretical Study Contribution towards Mechanism Elucidation

“…The final pathway is related to the intramolecular proton transfer with the production of pyrimidinone. Several hypothesis may arise for this process, the most favourable process being the proton transfer (atom 10) from atom C (7) to N(1). The proton transfer is postulated to occur at the triplet state, and by intersystem crossing it goes to the singlet state.…”

“…Tetrazoles are synthetic molecules containing a cyclic system with high aromaticity formed by four nitrogen atoms and one carbon atom [1,2]. Tetrazoles are being used in medicinal chemistry as bioisostere for carboxylic acids, as they originate from similar receptor-ligand interactions [3], as well as drugs in the treatment of several diseases, due the diversity of physical-chemical properties [4][5][6][7]. The energy materials industry also uses tetrazolic compounds as they are rich in nitrogen [8], have a high value of enthalpy of formation, thermal stability, explosive performance, and low sensitivity [9].…”

Quantified Piper sarmentosum Roxb. Leaves Aqueous Leaf Extract and Its Antihypertensive Effect in Dexamethasone-Induced Hypertensive Rats

“…The dosage of AEPS2 proven to attenuate hypertension in spontaneously hypertensive rats (SHRs) (Zainudin et al 2015) and L-N G -nitro arginine methyl ester (L-NAME)-induced hypertensive rats (Nik Mohd Alwi et al 2018) was selected. SHR is the gold standard animal model for studying hypertension (Trindade et al 2018), whereas L-NAME is widely used to create a NO-deficient hypertension model (Vrankova et al 2019). One of the mechanisms of dexamethasone-induced hypertension is through NO reduction (Huyut et al 2018); thus, we chose our AEPS dose based on the aforementioned studies.…”

Pharmacological evaluation of the hydro-alcoholic extract of Campomanesia phaea fruits in rats

“…The systolic blood pressure (SBP) of the rats was measured using a non-invasive method (Alexander, 1957;Trindade et al, 2018;Aekthammarat et al, 2019). Initially, the animals were treated daily with distilled water (5mL/Kg, p.o.)…”