title: A vasoactive role for endogenous relaxin in mesenteric arteries of male mice.
abstract: 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 µM). 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.
authors.affiliation: Department of Zoology, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Chen Huei
authors.initials: CH
authors.lastname: Leo
authors.affiliation: Department of Zoology, The University of Melbourne, Parkville, VIC, Australia; Department of Physiology, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Jelinic
authors.affiliation: Department of Zoology, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Jon H
authors.initials: JH
authors.lastname: Gooi
authors.affiliation: Department of Physiology, Monash University, Clayton, VIC, Australia.
authors.forename: Marianne
authors.initials: M
authors.lastname: Tare
authors.affiliation: Department of Zoology, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Parry
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010656:Phenylephrine / Q000494:pharmacology; D012065:Relaxin / Q000235:genetics / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D012065:Relaxin