TY - JOUR
T1 - Vasorelaxant effect in rat aortic rings through calcium channel blockage
T2 - A preliminary in vitro assessment of a 1,3,4-oxadiazole derivative
AU - Bankar, Girish R.
AU - Nandakumar, K.
AU - Nayak, Pawan G.
AU - Thakur, Anjali
AU - Chamallamudi, Mallikarjuna Rao
AU - Nampurath, Gopalan Kutty
PY - 2009/10/30
Y1 - 2009/10/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70249122305&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70249122305&partnerID=8YFLogxK
U2 - 10.1016/j.cbi.2009.07.014
DO - 10.1016/j.cbi.2009.07.014
M3 - Article
C2 - 19643099
AN - SCOPUS:70249122305
SN - 0009-2797
VL - 181
SP - 377
EP - 382
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
IS - 3
ER -