Vasorelaxant effect in rat aortic rings through calcium channel blockage: a preliminary in vitro assessment of a 1,3,4-oxadiazole derivative.
The study was undertaken on the basis of several reports in the literature that relaxation of vascular smooth muscles is a good treatment strategy in hypertension, angina and other cardiovascular disorders. Oxadiazoles have been reported to have effect on vascular smooth muscles and calcium influx. The goals of our current in vitro study were to investigate the effect of a 1,3,4-oxadiazole derivative on vascular smooth muscles in rat aorta, and to elucidate the associated signaling pathway. NOX-1 induced a relaxation of vascular smooth muscles in both endothelium intact and denuded rat aortic rings precontracted with norepinephrine or phenylephrine or KCl. NOX-1 also significantly antagonized cumulative dose-response effect of norepinephrine, phenylephrine, KCl or calcium with reduction in submaximal contractions. Verapamil, an L-type of calcium channel blocker, effectively attenuated phenylephrine and calcium induced contractions in aortic rings. Incubation with NOX-1 and verapamil did not significantly alter the dose-response curve of phenylephrine or calcium compared to verapamil treatment alone indicating L-type Ca2+ channel blockage leads to loss of NOX-1 activity. Hence it can be concluded NOX-1 exhibited vasorelaxant action by inhibiting calcium influx from extracellular space to intracellular space through L-type of calcium channels.
Bankar
Girish R
GR
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Madhav Nagar, Manipal-576104, Karnataka, India.
Nandakumar
K
K
Nayak
Pawan G
PG
Thakur
Anjali
A
Chamallamudi
Mallikarjuna Rao
MR
Nampurath
Gopalan Kutty
GK
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D014664:Vasodilation / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010069:Oxadiazoles; D010656:Phenylephrine; D011189:Potassium Chloride; D014700:Verapamil; D009638:Norepinephrine