The effect of vericiguat cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit

Background Cerebral vasospasm following subarachnoid hemorrhage is a clinically extremely serious complication associated with high morbidity and mortality. Our study investigated effects of vericiguat in a rabbit model of subarachnoid hemorrhage. Methods Fifty adult male New Zealand white rabbits were randomly divided into five groups: group 1 (control), group 2 (sham), group 3 (subarachnoid hemorrhage), group 4 (treatment of low-dose vericiguat), group 5 (treatment of high-dose vericiguat). We conducted measurements of basilar artery dimensions and performed histopathological assessments and oxidative stress tests and nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway protein evaluations and inflammatory cytokine and apoptotic marker assessments. Results In group 3, the vasospasm index was found to be 43.62%, while with high-dose vericiguat administration, this value decreased to 14.16% (p < 0.001). The total histopathological score decreased from 12 to 4. Although brain cGMP levels decreased by 66% in the group 3, they were recovered by 87% after treatment. Malondialdehyde levels decreased from 2.7 times to 1.5 times in the control group, while superoxide dismutase activity approached normal values. Tumor necrosis factor-alpha and interleukin-1 beta levels decreased by more than half. The apoptotic index decreased from 24.8% to 8.4%, while neurological scores showed significant improvement. Conclusions Our findings demonstrated that vericiguat effectively treated cerebral vasospasm through its ability to alter NO–sGC–cGMP signaling pathways and its reduction of oxidative stress and inflammation which resulted in neuronal protection. In conclusion, the vericiguat treatment might be beneficial in preventing vasospasm after subarachnoid haemorrhage, thus showing potential for clinical application.