Involvement of TRPV1-containing peripheral sensory efferents in hemodynamic responses in a rat hemorrhagic shock model

Background: Mechanisms underlying hemodynamic disturbance in hemorrhagic shock are not completely understood. Transient receptor potential vanilloid 1-expressing afferents are involved in hemorrhagic shock pathology, and transient receptor potential vanilloid 1 antagonist, capsazepine, acts on the central nervous system to improve mortality in a rat hemorrhagic shock model. In contrast, transient receptor potential vanilloid 1-positive efferents promote vasoactive reactions through the release of neuropeptides, including calcitonin gene-related peptides. This study aimed to investigate whether transient receptor potential vanilloid 1-positive peripheral sensory efferents are involved in hemodynamic responses after hemorrhagic shock. Methods: Male rats underwent hemorrhagic shock (mean arterial pressure 30 mm Hg for 90 min, followed by resuscitation for 30 min) and received capsazepine (5 mu M/kg) 30 min after shock induction. A separate cohort of rats subjected to hemorrhagic shock received hCGRP(8-37) (300 mu g/kg), a calcitonin gene-related peptide receptor antagonist, at 30, 60, or 90 minutes after shock induction. The 24-hour survival rate, mean arterial pressure, heart rate, arterial blood gas, and plasma calcitonin gene-related peptide levels were measured. Tissue blood flow and oxygenation both in the mesentery and skeletal muscle were also assessed. Results: Capsazepine treatment prevented the hemorrhagic shock-induced increase in plasma calcitonin gene-related peptide levels, and hCGRP(8-37) treatment improved the 24-h survival rates after hemorrhagic shock at a time-dependent manner. The hCGRP(8-37)- or capsazepine-treated rats exhibited tissue oxygenation and metabolic conditions comparable to those in control rats at the end of the experiment. Conclusion: Transient receptor potential vanilloid 1 plays a crucial role in hemodynamic responses to hemorrhagic shock, partly via calcitonin gene-related peptide release, involved in its peripheral sensory efferent functions. The hCGRP(8-37) appears to improve peripheral circulatory failure, which may be useful as adjunct treatment after hemorrhagic shock. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

This study investigated the role of TRPV1-positive peripheral sensory efferents in hemodynamic responses after hemorrhagic shock. The findings suggest that the TRPV1 antagonist capsazepine and the calcitonin gene-related peptide receptor antagonist hCGRP(8-37) can improve survival rates after hemorrhagic shock and maintain tissue oxygenation and metabolic conditions.