Effects of tetramethylpyrazine on nitric oxide/cGMP signaling after cerebral vasospasm in rabbits.
Tetramethylpyrazine (TMP), an ingredient of Chinese herbal Szechwan lovage rhizome, shows vasorelaxant effect. Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is associated with high mortality and morbidity. Here, we evaluated the effect of TMP in a model of CVS and sought to identify the underlying mechanisms of action. A rabbit SAH model was established by injection of the autoblood via cisterna magna. Cerebral blood flow and arterial diameter were measured by Transcranial Doppler (TCD) and Computed Tomography Angiography (CTA). Expression of eNOS and PDE-V in basilar artery (BA) was assessed by western blots. Levels of nitric oxide (NO) in plasma and cerebral spinal fluid, and of intra-endothelium Ca(2+) were measured. Significantly reduced diameter and accelerated blood flow velocity were detected in BAs of SAH animals (P<0.05 vs. sham group). Expression of eNOS and NO was increased, and PDE-V expression was reduced by TMP.TMP ameliorated cerebral vasospasm (P<0.05 vs. SAH group), and L-NAME (a NOS inhibitor) partly abrogated the effects of TMP. TMP induced a dose-dependent increase of intra-endothelium Ca(2+). The current results demonstrated that the vasorelaxant effect of TMP was at least in part via regulation of NO/cGMP signaling.
Shao
Zhengkai
Z
Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nan Gang District, Harbin, Heilongjiang 150001, PR China.
Li
Jingwen
J
Zhao
Zhenhuan
Z
Gao
Cheng
C
Sun
Zhe
Z
Liu
Xiangzhen
X
D000818:Animals; D001488:Basilar Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D020013:Calcium Signaling / Q000187:drug effects; D002533:Cerebral Angiography; D006152:Cyclic GMP / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D009569:Nitric Oxide / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D017585:Ultrasonography, Doppler, Transcranial; D014665:Vasodilator Agents / Q000494:pharmacology*; D020301:Vasospasm, Intracranial / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
D011719:Pyrazines; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP; C017953:tetramethylpyrazine