Nitric oxide effects depend on different mechanisms in different regions of the rat heart |
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Authors: | Kursat Derici Ufuk Samsar Emine Demirel-Yilmaz |
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Institution: | (1) Department of Medical Pharmacology, Faculty of Medicine, Ankara University, Sihhiye, 06100 Ankara, Turkey; |
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Abstract: | The important role of nitric oxide (NO) in regulating cardiac functions has been investigated in prior research. However,
NO-induced signaling mechanisms in the different regions of the heart have not been explored until now. In this study, the
mechanism of NO effects on the spontaneously beating right atrium and left papillary muscle isolated from the rat heart was
examined. The NO donor diethylamine NONOate (DEA/NO) (0.1–100 μM) depressed the resting and developed tensions, as well as
the sinus rate, of the right atrium. The effect of DEA/NO on contractions of the right atrium was blocked by the soluble guanylate
cyclase (sGC) inhibitor, ODQ (1H-1,2,4]oxadiazolo4,3-α]quinoxalin-1-one) (10 μM). The ATP-sensitive potassium channel (KATP) blocker glyburide (3 μM) reversed DEA/NO-induced decreases in the resting tension. The suppressor effect of DEA/NO on the
sinus rate was inhibited only by the superoxide radical scavenger superoxide dismutase (25 U/ml). Neither the cGMP-dependent
protein kinase (PKG) inhibitor KT5823 (0.1 μM) nor the cAMP-dependent protein kinase (PKA) inhibitor KT5720 (1 μM) changed
DEA/NO responses in the right atrium. While the resting tension of the right atrium was decreased by the NO precursor l-arginine (1–100 μM), it was increased by the nitric oxide synthase inhibitor l-NMMA (0.1–100 μM). The sinus rate was not affected by l-arginine or l-NMMA. The left papillary muscle contraction was not influenced by any of these NO-related agents. These results show that
high concentration NO-induced depression of the contraction of the right atrium is due to sGC and KATP channel activation, but suppression of the sinus rate depends on redox regulation. Our results may have important implications
for the region-dependent functional disability of cardiac myocytes, as well as the regulation of heart performance in high
NO-induced pathological conditions. |
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