Pellegrino D, Palmerini C A, Tota B
Department of Pharmaco-Biology, University of Calabria, 87030, Arcavacata di Rende, CS, Italy.
J Exp Biol. 2004 Oct;207(Pt 22):3855-64. doi: 10.1242/jeb.01180.
The role of nitric oxide (NO) in cardio-vascular homeostasis is now known to include allosteric redox modulation of cell respiration. An interesting animal for the study of this wide-ranging influence of NO is the cold-adapted Antarctic icefish Chionodraco hamatus, which is characterised by evolutionary loss of hemoglobin and multiple cardio-circulatory and subcellular compensations for efficient oxygen delivery. Using an isolated, perfused working heart preparation of C. hamatus, we show that both endogenous (L-arginine) and exogenous (SIN-1 in presence of SOD) NO-donors as well as the guanylate cyclase (GC) donor 8Br-cGMP elicit positive inotropism, while both nitric oxide synthase (NOS) and sGC inhibitors, i.e. L-NIO and ODQ, respectively, induce significant negative inotropic effects. These results therefore demonstrate that under basal working conditions the icefish heart is under the tonic influence of a NO-cGMP-mediated positive inotropism. We also show that the working heart, which has intracardiac NOS (shown by NADPH-diaphorase activity and immunolocalization), can produce and release NO, as measured by nitrite appearance in the cardiac effluent. These results indicate the presence of a functional NOS system in the icefish heart, possibly serving a paracrine/autocrine regulatory role.
一氧化氮（NO）在心血管稳态中的作用现已明确包括对细胞呼吸的变构氧化还原调节。对于研究NO的这种广泛影响而言，一种有趣的动物是适应寒冷的南极冰鱼——带纹南极鱼，其特征是在进化过程中血红蛋白缺失，并具有多种心血管循环和亚细胞层面的补偿机制以实现高效的氧气输送。通过使用带纹南极鱼的离体灌注工作心脏标本，我们发现内源性（L-精氨酸）和外源性（超氧化物歧化酶存在下的SIN-1）NO供体以及鸟苷酸环化酶（GC）供体8Br-cGMP均能引发正性肌力作用，而一氧化氮合酶（NOS）抑制剂L-NIO和可溶性鸟苷酸环化酶（sGC）抑制剂ODQ分别诱导出显著的负性肌力作用。因此，这些结果表明，在基础工作条件下，冰鱼心脏受到NO-cGMP介导的正性肌力作用的紧张性影响。我们还表明，具有心内NOS（通过NADPH-黄递酶活性和免疫定位显示）的工作心脏能够产生并释放NO，这可通过心脏流出物中亚硝酸盐的出现来测量。这些结果表明冰鱼心脏中存在功能性NOS系统，可能发挥旁分泌/自分泌调节作用。
