Vasodilation and hypotension of a novel 3-benzylquinazolin- 4(3H)-one derivative via the inhibition of calcium flux
| Autor: | Sai-Jie Zuo, Dong-Zheng Liu, Lei Cao, San-Qi Zhang, Sen Li, Yong-Xiao Cao |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Potassium Channels Vasodilator Agents chemistry.chemical_element Vasodilation Calcium Pharmacology Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Soluble Guanylyl Cyclase Calcium flux medicine Animals Mesenteric arteries Phenylephrine Antihypertensive Agents Protein Kinase C Quinazolinones Chemistry Biological Transport Tetraethylammonium chloride Protein-Tyrosine Kinases Mesenteric Arteries Rats Sarcoplasmic Reticulum 030104 developmental biology medicine.anatomical_structure Anesthesia Prostaglandins Endothelium Vascular Nitric Oxide Synthase Soluble guanylyl cyclase Artery medicine.drug |
| Zdroj: | European journal of pharmacology. 791 |
| ISSN: | 1879-0712 |
| Popis: | A novel 3-benzylquinazolin-4(3H)-one derivative Z32, namely 6,7-dimethoxy-3-(3-chloro-4-(4-fluorobenzyloxy)benzyl)quinazolin-4(3H)-one was synthesized. The vasorelaxant and antihypertensive effects of Z32 and its underlying mechanisms were investigated. The following methods were used. The isometric tension of artery ring segments was recorded using an in vitro myography system. Changes in the calcium influx in mesenteric arteries were surveyed using a real-time confocal microscopy. The arterial pressure of spontaneously hypertensive rats was measured in vivo using a non-invasive tail cuff blood pressure system. The results showed that Z32 can relax rat mesenteric arteries pre-constricted by KCl or phenylephrine in a concentration-dependent manner. The vasorelaxant effects were not affected by the removal of the endothelium, blockade of potassium channels by tetraethylammonium chloride, or inhibition of either guanylate cyclase by ODQ, nitric oxide synthase by l-NAME, or cyclooxygenase by indomethacin. In Ca2+-free conditions, Z32 did not affect the constriction evoked by caffeine, however, significantly reduced the constrictions induced (1) by phenylephrine, (2) by CaCl2 in either phenylephrine (in the presence of verapamil) or KCl stimulated arteries, (3) by extracellular Ca2+ restoration in thapsigargin-treated mesenteric arteries, and (4) by the activator of protein kinase C phorbol-12, 13-dibutyrate, and the inhibitor of protein tyrosine phosphatase sodium orthovanadate. Further, Z32 decreased the systolic and diastolic arterial pressure of spontaneously hypertensive rats in a dose-dependent manner. In conclusion, Z32 lowers the arterial pressure and induces vasorelaxation through the inhibition of calcium flux, probably via a protein tyrosine phosphorylation-dependent way. |
| Databáze: | OpenAIRE |
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