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T18/S19 diphosphorylation of myosin regulatory Light Chain is Responsible for the impaired relaxation of pulmonary arteries in pulmonary hypertensive rats
Author(s) -
Cho Suhan,
Oh Seung Beom,
Kim Sung Joon
Publication year - 2022
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.2022.36.s1.r2088
Subject(s) - rho associated protein kinase , electrical impedance myography , rhoa , myosin light chain kinase , contraction (grammar) , sodium nitroprusside , soluble guanylyl cyclase , myosin light chain phosphatase , chemistry , mesenteric arteries , medicine , endocrinology , rho kinase inhibitor , myosin , nitric oxide , vasodilation , pharmacology , signal transduction , artery , biochemistry , guanylate cyclase
Pulmonary arteries (PA) are exposed to hemodynamic environment and contractile stimuli different from those of systemic arteries. Previous studies reported that in situ application of sodium nitroprusside (SNP, NO donor) lowered the PA pressure, which was less prominent than the response of systemic arteries. Here, we investigated the relaxation speed and the in vitro effects of NO‐dependent signaling modulators to compare between isolated PA and mesenteric arteries (MA) of rats. In the dual‐wire myography study, PA showed significantly slower relaxation after the response to 80 mM KCl (80K) or to pharmacological agonists (U46619 and PGF2a). Surprisingly, addition of 30 mM SNP could not prevent the 80K contraction in PA while significantly attenuated the contraction of MA. The pretreatment with soluble guanylate cyclase (sGC) inhibitor (ODQ, 10 mM) markedly further slowed the relaxation of PA after 80K or agonist‐induced contraction. Perplexingly, immunoblot assay revealed higher expression of sGC‐a with similar level of sGC‐b1 in PA than MA. The expression of RhoA‐kinase (ROCK) was higher while myosin light chain phosphatase (MYPT) appeared lower in PA than MA. The treatment with ROCK inhibitor (Y27632, 10 mM) could abolish the different of relaxation response between PA and MA. Taken together, we speculate that despite the higher expression and the functional importance of NO/sGC pathway in PA, the higher level of ROCK and relatively low MYPT in PA are responsible for the characteristic slow relaxation after removal of stimuli.