A Vasoactive Role for Endogenous Relaxin in Mesenteric Arteries of Male Mice |
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Authors: | Chen Huei Leo Maria Jelinic Jon H Gooi Marianne Tare Laura J Parry |
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Institution: | 1. Department of Zoology, The University of Melbourne, Parkville, VIC, Australia.; 2. Department of Physiology, The University of Melbourne, Parkville, VIC, Australia.; 3. Department of Physiology, Monash University, Clayton, VIC, Australia.; University of Padua, Italy, |
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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 {"type":"entrez-nucleotide","attrs":{"text":"U41669","term_id":"1195477","term_text":"U41669"}}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. |
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