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Effect of molsidomine and tempol on ischemic tolerance of chronically hypoxic rat hearts
Author(s) -
Mandikova Petra,
Micova Petra,
Kozichova Kristyna,
Dabrowska Ludmila,
Kolar Frantisek,
Neckar Jan
Publication year - 2012
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.26.1_supplement.1137.10
Subject(s) - molsidomine , medicine , cardioprotection , nitric oxide , ischemia , cardiology , reactive oxygen species , myocardial infarction , hypoxia (environmental) , anesthesia , oxygen , pharmacology , chemistry , biochemistry , organic chemistry
Chronic hypoxia (CH) is associated with increased formation of reactive oxygen species (ROS), pulmonary hypertension (PH) and improved myocardial tolerance to ischemia/reperfusion injury. The aim was to find out whether nitric oxide donor (molsidomine; MOL) and superoxide dismutase mimetic (tempol; TMP) attenuate i) development of PH and ii) increased ischemic tolerance of CH hearts. Adult male Wistar rats were adapted to continuous normobaric CH (10 % O2, 4 wks). Subgroups of the animals were treated with MOL or TMP given either acutely before ischemia or chronically during adaptation. Right ventricular systolic pressure (RVSP) was increased in CH rats by 70 % compared to the normoxic group. Chronic TMP significantly attenuated the increase in RVSP while no effect was observed in chronic MOL‐treated group. Adaptation to CH significantly decreased infarct size induced by coronary artery occlusion (43.4 ± 2.9 % of the area at risk) compared to normoxic controls (57.5 ± 2.7 %). Chronic TMP abolished the protection induced by CH (55.3 ± 2.6 %). Acute TMP had any effect on infarct size in neither group. Chronic MOL reduced infarct size only in the normoxic group (50.7 ± 2.3 %) while acute MOL treatment protected both normoxic and CH groups by 40 – 45 %. Our results confirm that ROS play a role in the development of PH and cardioprotection induced by CH. Supported by grants IAAX01110901 and GAUK 411911.