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https://hdl.handle.net/2440/122826
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Type: | Journal article |
Title: | Relaxin reduces endothelium-derived vasoconstriction in hypertension: revealing new therapeutic insights |
Author: | Leo, C.H. Ng, H.H. Marshall, S.A. Jelinic, M. Rupasinghe, T. Qin, C. Roessner, U. Ritchie, R.H. Tare, M. Parry, L.J. |
Citation: | British Journal of Pharmacology, 2019; 177(1):1-17 |
Publisher: | Wiley |
Issue Date: | 2019 |
ISSN: | 0007-1188 1476-5381 |
Statement of Responsibility: | Chen Huei Leo, Hooi Hooi Ng, Sarah A. Marshall, Maria Jelinic, Thusitha Rupasinghe ... Laura J. Parry ... et al. |
Abstract: | BACKGROUND AND PURPOSE:Endothelium-derived vasoconstriction is a hallmark of vascular dysfunction in hypertension. In some cases, an overproduction of endothelium-derived prostacyclin (PGI2 ) can cause contraction rather than relaxation. Relaxin is well known for its vasoprotective actions, but the possibility that this peptide could also reverse endothelium-derived vasoconstriction has never been investigated. We tested the hypothesis that short-term relaxin treatment mitigates endothelium-derived vasoconstriction in spontaneously hypertensive rats (SHR). EXPERIMENTAL APPROACH:Male Wistar Kyoto rats (WKY) and SHR were subcutaneously infused with either vehicle (20 mmol·L-1 sodium acetate) or relaxin (13.3 μg·kg-1 ·hr-1 ) using osmotic minipumps for 3 days. Vascular reactivity to the endothelium-dependent agonist ACh was assessed in vitro by wire myography. Quantitative PCR and LC-MS were used to identify changes in gene expression of prostanoid pathways and PG production, respectively. KEY RESULTS:Relaxin treatment ameliorated hypertension-induced endothelial dysfunction by increasing NO-dependent relaxation and reducing endothelium-dependent contraction. Notably, short-term relaxin treatment up-regulated mesenteric PGI2 receptor (IP) expression, permitting PGI2 -IP-mediated vasorelaxation. In the aorta, reversal of contraction was accompanied by suppression of the hypertension-induced increase in prostanoid-producing enzymes and reduction in PGI2 -evoked contractions. CONCLUSIONS AND IMPLICATIONS:Relaxin has region-dependent vasoprotective actions in hypertension. Specifically, relaxin has distinct effects on endothelium-derived contracting factors and their associated vasoconstrictor pathways in mesenteric arteries and the aorta. Taken together, these observations reveal the potential of relaxin as a new therapeutic agent for vascular disorders that are associated with endothelium-derived vasoconstriction including hypertension. |
Keywords: | Mesenteric Arteries Endothelium, Vascular Animals Rats, Inbred SHR Rats, Inbred WKY Rats Hypertension Relaxin Vasoconstriction Dose-Response Relationship, Drug Male |
Description: | First published: 03 September 2019 |
Rights: | © 2019 The British Pharmacological Society. |
DOI: | 10.1111/bph.14858 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1059960 |
Published version: | http://dx.doi.org/10.1111/bph.14858 |
Appears in Collections: | Aurora harvest 8 Pharmacology publications |
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