Mikawa K, Kume H, Takagi K
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Arzneimittelforschung. 1998 Sep;48(9):914-8.
The relaxant effects of intracellular concentration of cyclic guanosine monophosphate (cGMP) on spontaneous tone in human tracheal smooth muscle were investigated in comparison with guinea pig, using isometric tension records. In both human and guinea pig tracheas, application of atrial natriuretic peptide (ANP) and 8-brom cGMP (a membrane permeable analogue of cGMP) caused an inhibition of spontaneous tone in a concentration-dependent fashion. However, ANP was less potent in relaxation of tracheal smooth muscle in human than guinea pigs, and values of % relaxation induced by 1 mmol/l ANP in human and guinea pigs were 37.1 +/- 5.3 and 82.7 +/- 10.5%, respectively (n = 6). In the presence of 30 nmol/l iberiotoxin (IbTX), a potent and selective large conductance Ca(2+)-activated K+ (BKCa) channel inhibitor, relaxant actions of ANP on human tracheal smooth muscle were markedly suppressed, and values of % relaxation by 1 mmol/l ANP decreased to 8.4 +/- 1.2% (n = 6). On the other hand, 8-brom cGMP was roughly equipotent in relaxating tracheal smooth muscle in these two species, different from ANP, and inhibitory effects of 8-brom cGMP on both human and guinea pig tracheal smooth muscle were also markedly suppressed in the presence of 30 nmol/l IbTX, similar to ANP. These results demonstrate that augmentation of BKCa channel activity may play a functionally important role in the cGMP-induced relaxation in human airway smooth muscle. However, ANP may have modest potency as a bronchodilator.
使用等长张力记录，比较了环磷酸鸟苷（cGMP）细胞内浓度对人气管平滑肌自发张力的舒张作用与豚鼠的情况。在人和豚鼠的气管中，应用心房利钠肽（ANP）和8-溴cGMP（cGMP的膜通透性类似物）均以浓度依赖性方式抑制自发张力。然而，ANP对人气管平滑肌的舒张作用比豚鼠弱，1 mmol/l ANP在人和豚鼠中诱导的舒张百分比分别为37.1±5.3%和82.7±10.5%（n = 6）。在存在30 nmol/l埃博毒素（IbTX）（一种强效且选择性的大电导钙激活钾（BKCa）通道抑制剂）的情况下，ANP对人气管平滑肌的舒张作用明显受到抑制，1 mmol/l ANP的舒张百分比降至8.4±1.2%（n = 6）。另一方面，与ANP不同，8-溴cGMP在这两个物种的气管平滑肌舒张中大致等效，并且在存在30 nmol/l IbTX的情况下，8-溴cGMP对人和豚鼠气管平滑肌的抑制作用也明显受到抑制，与ANP相似。这些结果表明，BKCa通道活性的增强可能在cGMP诱导的人气道平滑肌舒张中发挥重要的功能作用。然而，ANP作为支气管扩张剂的效力可能适中。
