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Roles of nNOS and eNOS in rat heart ; comparison between the left and right ventricle myocytes
Author(s) -
Kwon Jaewon
Publication year - 2020
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.2020.34.s1.05026
Subject(s) - ventricle , myocyte , medicine , contractility , enos , contraction (grammar) , endocrinology , sarcomere , chemistry , cardiology , nitric oxide synthase , nitric oxide
Right ventricle (RV) has physiological as well as anatomical differences compared with left ventricle (LV). There are constitutive NO synthase isoforms, neuronal NOS (nNOS) and endothelial NOS (eNOS) in myocardium, regulating the calcium dynamics and contractility. Here we compared the roles of nNOS and eNOS in the RV and LV myocytes from S‐D rats. After isolating the myocytes using Langendorff perfusion system, their sarcomere shortening and [Ca 2+ ] i were simultaneously measured using the Ionoptix system while paced by 2 Hz field stimulation. nNOS‐specific inhibitor, S‐methyl‐L‐thiocitrulline (SMTC) and the non‐specific NOS inhibitor, L‐NG‐Nitroarginine methyl ester (L‐NAME) were used to pharmacologically dissect the roles of NOS isoforms. According to the immunoblot assay, the protein amounts of nNOS and its phosphorylated form were not different between RV and LV. Although the amount of eNOS was lower in RV than LV, its phosphorylated form was similar. RV myocytes showed slower contraction (longer T Peak ) and slower relaxation (longer T relax ) than LV myocytes. The treatment with SMTC or L‐NAME shortened T Peak and T relax of RV myocytes, abolishing the kinetic differences of ΔSL. It was notable that the T relax of LV myocytes became slightly longer by SMTC. Paradoxically, the length of sarcomere shortening (ΔSL) was increased while the amplitude of calcium transient (Δ[Ca 2+ ] i ) was decreased by SMTC in RV myocytes. However, SMTC did not affect the ΔSL and Δ[Ca 2+ ] i of LV myocytes. Our study suggest that the slower contraction and relaxation of RV myocytes might be partly due to differential responses to the nNOS‐dependent intracellular signaling. The opposite direction of changes in the amplitudes of ΔSL and Δ[Ca 2+ ] i by SMTC suggest that the nNOS in RV myocytes is responsible for negative inotropy despite the positive effects on the calcium transient, which is not evident in LV myocytes.