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RELAXIN (Rlx) MEDIATED FAST RELAXATION OF ARTERIES THROUGH PI3 KINASE AND NITRIC OXIDE
Author(s) -
Novak Jacqueline,
Rubin J Peter,
Matthews Julianna,
Conrad Kirk P
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1371-b
Subject(s) - vasodilation , coronary arteries , endocrinology , constriction , chemistry , nitric oxide , medicine , mesenteric arteries , relaxation (psychology) , electrical impedance myography , artery
The vasodilatory mechanisms of Rlx depend on the duration of exposure to hormone. Fast relaxation to Rlx was reported for human pre‐constricted gluteal, but not pulmonary arteries, that was abolished by endothelial removal (C Fisher et al. Circ. 106:, 2002). We studied small coronary, mesentery and renal arteries from rats, as well as human subcutaneous arteries. The arteries were mounted in a pressure arteriograph, and after pre‐constriction to EC 50 with phenylephrine, they were incubated with increasing concentrations of recombinant human (rh) Rlx from 1 to 100 ng/ml (maximum relaxation in < 5 min). Only small renal arteries showed a concentration dependent relaxation (p<0.001 by ANOVA) with a maximum relaxation of 20–30% at the highest rhRlx dose which was abolished by prior endothelial removal or by pre‐incubation with 0.1mM L‐NMA (p<0.001 by ANOVA vs without L‐NMA). Pre‐treatment with the PI3 kinase inhibitors, LY294002 (3μM) or Wortmannin (10nM), attenuated relaxation by ~ 80% (p<0.05 by ANOVA vs dilute DMSO vehicle). Human subcutaneous arteries also showed a concentration dependent relaxation (p<0.001 by ANOVA) with a maximum relaxation of 60–80% at the highest rhRlx dose. In preliminary studies, this rapid vasodilatory response to rhRlx in human subcutaneous arteries was completely inhibited by both L‐NMA and LY294002. In conclusion, some rat and human arteries show a fast relaxation response to Rlx mediated by PI3 kinase and NO.