C-Type Natriuretic Peptide Induces Anti-contractile Effect Dependent on Nitric Oxide, Oxidative Stress, and NPR-B Activation in Sepsis

Abstract

Aims: To evaluate the role of nitric oxide, reactive oxygen species (ROS), and natriuretic peptide receptor-B activation in C-type natriuretic peptide-anti-contractile effect on Phenylephrine-induced contraction in aorta isolated from septic rats.Methods and Results: Cecal ligation and puncture (CLP) surgery was used to induce sepsis in male rats. Vascular reactivity was conducted in rat aorta and resistance mesenteric artery (RMA). Measurement of survival rate, mean arterial pressure (MAP), plasma nitric oxide, specific protein expression, and localization were evaluated. Septic rats had a survival rate about 37% at 4 h after the surgery, and these rats presented hypotension compared to control-operated (Sham) rats. Phenylephrine-induced contraction was decreased in sepsis. C-type natriuretic peptide (CNP) induced anti-contractile effect in aortas. Plasma nitric oxide was increased in sepsis. Nitric oxide-synthase but not natriuretic peptide receptor-B expression was increased in septic rat aortas. C-type natriuretic peptide-anti-contractile effect was dependent on nitric oxide-synthase, ROS, and natriuretic peptide receptor-B activation. Natriuretic peptide receptor-C, protein kinase-Cα mRNA, and basal nicotinamide adenine dinucleotide phosphate (NADPH)-dependent ROS production were lower in septic rats. Phenylephrine and CNP enhanced ROS production. However, stimulated ROS production was low in sepsis.Conclusion: CNP induced anti-contractile effect on Phenylephrine contraction in aortas from Sham and septic rats that was dependent on nitric oxide-synthase, ROS, and natriuretic peptide receptor-B activation.

A natriuretic peptide from Arabidopsis thaliana (AtPNP-A) can modulate catalase 2 activity

“…via the modulation of the plasma membrane NADPH oxidase by AtPNP-A. However, neither NADPH oxidases nor peroxidases, enzymes responsible for ROS generation upon pathogen attack 67 , have been identified in our protein–protein interaction studies, although animal analogues of PNP have been shown or speculated to activate NADPH oxidase 68 , 69 . Instead, we identified CAT2 (Fig.…”

Defective development and microcirculation of intestine in Npr2 mutant mice

“…Recent studies have suggested that CNP is related to inflammation. For example, CNP plasma concentrations increased in humans and rats with organ dysfunction caused by sepsis-related inflammation 38,39 . However, CNP plasma levels were indistinguishable between control and Npr2 slw/slw mice.…”

B-type natriuretic peptide is upregulated by c-Jun N-terminal kinase and contributes to septic hypotension

“…These findings suggest that other pathways that signal through cGMP may still be active. Nevertheless, activation of NO signaling and activation of NPR-B by C-type natriuretic peptide, both of which stimulate guanylate cyclase, have previously been identified as major pathophysiological signaling pathways in sepsis (55)(56)(57). Sustained activation of these pathways may account for the partial increase in cGMP in BNP-KO mice and in mice treated with SP600125 or 19B3.…”