(715.3) Role of Rho-associated kinase (ROCK) in the different speed of relaxation between pulmonary arteries and mesentery arteries of rats

Poster Board Number: E80

Suhan Cho (Seoul National University Colledge of Medicine), Seung Beom Oh (Seoul National University Colledge of Medicine), Sung Joon Kim (Seoul National University Colledge of Medicine, Ischemic/Hypoxic Disease Institute)

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.

Support or Funding Information

This work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT of the Republic of Korea (grant no.NRF2021R1A2C200724311).