• Karla L Guarido, Ronald P M Gonçalves, Arquimedes Gasparotto Júnior, and José Eduardo da Silva-Santos.
• 1Department of Pharmacology, Laboratory of Cardiovascular Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil. 2Institute of Biological Sciences, Medical and Health, Universidade Paranaense, Umuarama, Parana, Brazil.
• Crit. Care Med.. 2014 Jun 1;42(6):e461-71.

ObjectiveWe evaluated the role of the renal vascular system and the Rho-A/Rho-kinase pathway in the maintenance of the pressor effects of vasopressin in endotoxemic rats.DesignIn vitro and in vivo animal study.SettingUniversity research laboratory.SubjectsMale Wistar rats (200-300 g).InterventionRats received either saline or lipopolysaccharide (10 mg/kg, intraperitoneal) 6 or 24 hours before the experiments. The effects of vasopressin on isolated aortic rings, cardiac function, mean arterial pressure, and both the renal vascular perfusion pressure of perfused kidneys in vitro and renal blood flow in situ were evaluated. The role of Rho-kinase in the renal and systemic effects of vasopressin was investigated through administration of the selective inhibitor Y-27632 and Western blot analysis.Measurements And Main ResultsThe effect of vasopressin on mean arterial pressure was unaltered and that on renal vascular perfusion pressure enhanced in endotoxemic rats at both 6 and 24 hours after lipopolysaccharide, despite reduced contractile responses in aortic rings and the lack of effect on cardiac function. Vasopressin (3, 10, and 30 pmol/kg, IV) produced increased reduction in renal blood flow in endotoxemic rats. In perfused kidneys from lipopolysaccharide groups, administration of Y-27632 reverted the hyperreactivity to vasopressin. Treatment with Y-27632 partially inhibited the effects of vasopressin on mean arterial pressure and significantly reduced the effects of vasopressin on renal blood flow in control but not in endotoxemic rats. Although the protein levels of Rho-A and Rho-kinase I and II had not been impaired, the levels of phosphorylated myosin phosphatase-targeting subunit 1, the regulatory subunit of myosin phosphatase that is inhibited by Rho-kinase, were increased in both the renal cortex and the renal medulla of endotoxemic rats.ConclusionOur data suggest that activation of Rho-kinase potentiates the vascular effects of vasopressin in the kidneys, contributing to the maintenance of the hypertensive effects of this agent during septic shock.

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