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 Ca2+ 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 Ca2+. The current results demonstrated that the vasorelaxant effect of TMP was at least in part via regulation of NO/cGMP signaling.

Research Highlights►TMP ameliorated cerebral vasospasm and increased expression of eNOS in basilar artery of rabbits. ►NO was increased in TMP treated animals and it may be mediated by upregulation of eNOS. ►TMP increased concentration of intra-endothelial Ca2+ and this may trigger the expression of eNOS.