Abstract 13733: Relaxin Deficiency Impairs Endothelial Function and Volume Compliance in Mesenteric Arteries of Males
The peptide hormone relaxin (RLX) and its receptor are expressed in arteries from males and females, suggesting an autocrine role for endogenous RLX in maintaining vascular homeostasis. RLX is an important vasodilatory hormone in females, and contributes to maternal vascular adaptations during pregnancy. However, less is known about the role of endogenous RLX in the regulation of vascular function in males. In this study male adult (~12 months old) wild-type (Rln WT) and RLX knockout mice (Rln KO) were used to test the hypothesis that vascular reactivity and compliance in mesenteric arteries are compromised in Rln KO mice. Vascular reactivity was analysed using wire myography and revealed that the responses to phenylephrine were significantly (P=0.001) increased in Rln KO mice (pEC50; 6.85±0.07, n=10) compared to wildtype males (6.49±0.04, n=7). Conversely, the sensitivity to the endothelium-dependent vasodilator, acetylcholine (ACh) was significantly (P=0.016) decreased in arteries from Rln KO (6.39±0.07, n=9) versus Rln WT mice (6.85±0.17, n=8). However, the responses to the endothelium-independent vasodilator, sodium nitroprusside were not affected by RLX deficiency, indicating a selective impairment of endothelial function. The abnormalities in the ACh response in Rln KO mice were reversed (6.81±0.09, n=5, P=0.005) in the presence of the cyclooxygenase inhibitor, indomethacin (2x10-6M), suggesting an up-regulation of vasoconstrictor prostanoids in Rln KO mice. Furthermore, ACh-induced endothelium-derived hyperpolarizing factor-type relaxation and nitric oxide-mediated relaxation were not affected by RLX deficiency. Volume compliance, assessed by pressure myography, was significantly (P<0.05) decreased in mesenteric arteries of Rln KO mice. In conclusion, RLX deficiency is associated with impaired endothelial function and reduced passive arterial wall compliance in male mice. Our study highlights a significant role for endogenous RLX in the maintenance of normal vascular function and wall compliance.
- © 2013 by American Heart Association, Inc.