First Author | Leo CH | Year | 2014 |
Journal | PLoS One | Volume | 9 |
Issue | 9 | Pages | e107382 |
PubMed ID | 25243460 | Mgi Jnum | J:223413 |
Mgi Id | MGI:5648786 | Doi | 10.1371/journal.pone.0107382 |
Citation | Leo CH, et al. (2014) A vasoactive role for endogenous relaxin in mesenteric arteries of male mice. PLoS One 9(9):e107382 |
abstractText | The peptide hormone relaxin has striking effects on the vascular system. Specifically, endogenous relaxin treatment reduces myogenic reactivity through nitric oxide (NO)-mediated vasorelaxation and increases arterial compliance in small resistance arteries. However, less is known about the vascular roles of endogenous relaxin, particularly in males. Therefore, we used male wild-type (Rln+/+) and relaxin knockout (Rln-/-) mice to test the hypothesis that passive wall properties and vascular reactivity in mesenteric arteries would be compromised in Rln-/- mice. Passive compliance was determined in arteries (n=8-9) mounted on a pressure myograph and in Ca2+-free Krebs containing 2 mM EGTA. Passive volume compliance was significantly (P=0.01) decreased in the mesenteric arteries of Rln-/- mice. Vascular reactivity was assessed using wire myography. In mesenteric arteries (n=5) of Rln-/- mice, there was a significant (P<0.03) increase in sensitivity to the vasoconstrictors phenylephrine and thromboxane-mimetic U41669. This enhanced responsiveness to vasoconstrictors was abolished by endothelial denudation, and attributed to impaired NO and prostanoid pathways in Rln-/- mice. Sensitivity to the endothelial agonist acetylcholine was significantly (n=7-9, P </= 0.03) decreased, and this was abolished in the presence of the cyclooxygenase inhibitor, indomethacin (2 microM). This indicates that prostanoid vasoconstrictor pathways were upregulated in the mesenteric arteries of Rln-/- mice. In summary, we demonstrate endothelial dysfunction and impaired arterial wall remodeling in male mice deficient in relaxin. Thus, our results highlight a role for endogenous relaxin in the maintenance of normal mesenteric artery structure and function in males. |