Abstract
The reduced pressure response to vasopressin during acute sepsis has directed our interest to the regulation of vasopressin V-1A receptors. Rats were injected with lipopolysaccharide for induction of experimental gram-negative sepsis. V-1A receptor gene expression was downregulated in the liver, lung, kidney, and heart during endotoxemia. Inasmuch as the concentrations of proinflammatory ...
Abstract
The reduced pressure response to vasopressin during acute sepsis has directed our interest to the regulation of vasopressin V-1A receptors. Rats were injected with lipopolysaccharide for induction of experimental gram-negative sepsis. V-1A receptor gene expression was downregulated in the liver, lung, kidney, and heart during endotoxemia. Inasmuch as the concentrations of proinflammatory cytokines such as interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma were highly increased during sepsis, the influence of these cytokines on V-1A receptor expression was investigated in primary cultures of hepatocytes and in the aortic vascular smooth muscle cell line A7r5. V-1A receptor expression was downregulated by the cytokines in a nitric oxide-independent manner. Blood pressure dose-response studies after injection of endotoxin showed a diminished responsiveness to the selective V-1 receptor agonist Phe(2),Ile(3),Orn(8)-vasopressin. Our data show that sepsis causes a downregulation of V-1A receptors and suggest that this effect is likely mediated by proinflammatory cytokines. We propose that this downregulation of V-1A receptors contributes to the attenuated responsiveness of blood pressure in response to vasopressin and, therefore, contributes to the circulatory failure in septic shock.
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