Nifedipine enhances cGMP production through the activation of soluble guanylyl cyclase in rat ventricular papillary muscle
Nifedipine enhances cGMP production through the activation of soluble guanylyl cyclase in rat ventricular papillary muscle
复制标题
硝苯地平通过激活大鼠心室乳头肌中的可溶性鸟苷酸环化酶来增强 cGMP 的产生
DOI：
10.1211/0022357055740
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发表时间：
2005
影响因子：
3.3
通讯作者：
S. Motomura
中科院分区：
文献类型：
--
作者：
K. Seya;K. Furukawa;Kazuhiko Yoshida;Reina Narita;S. Motomura
硝苯地平是一种L型钙通道阻滞剂，可以增加cGMP的产生，这在一定程度上有助于血管平滑肌的松弛。我们研究的目的是澄清硝苯地平是否调节cGMP的产生，cGMP在心肌中具有生理作用。为了测量收缩反应和组织cGMP水平，将雄性Wistar大鼠制备的左心室乳头肌（350-400 g）在等长条件下置于离体器官室，并通过铂点电极（1hz， 1ms持续时间）进行电节奏。在乳头肌制备中，硝苯地平（30 ~ 300 nm）诱导的负性肌力效应在可溶性冠酰环化酶抑制剂ODQ （1H‐[1,2,4]oxidazolo[4,3‐a]quinoxaline‐1‐one; 10 μm）的存在下被显著抑制。此外，硝苯地平（100 nm）强烈增加组织cGMP水平，ODQ存在时cGMP水平显著降低。另一方面，一氧化氮合酶抑制剂NG -单甲基- 1 -精氨酸（100 μm）对硝苯地平诱导的负性肌力效应和cGMP的产生没有抑制作用。上述结果表明，硝苯地平对大鼠左心室乳头肌的负性肌力作用至少部分是通过直接激活心脏可溶性胍基环化酶而非一氧化氮合酶来增强的。
It is known that nifedipine, an L‐type calcium channel blocker, increases cGMP production, which partially contributes to the relaxation of vascular smooth muscle. The aim of our investigation was to clarify whether or not nifedipine regulates cGMP production, which has a physiological role in cardiac muscle. To measure contractile responses and tissue cGMP levels, left ventricular papillary muscles prepared from male Wistar rats (350–400 g) were mounted in the isolated organ chamber under isometric conditions and electrically paced by means of platinum punctate electrodes (1 Hz, 1 ms duration). In papillary muscle preparation, the negative inotropic effect induced by nifedipine (30 to 300 nm) was significantly inhibited in the presence of ODQ (1H‐[1,2,4]oxidazolo[4,3‐a]quinoxaline‐1‐one; 10 μm), a soluble guanylyl cyclase inhibitor. Furthermore, nifedipine (100 nm) strongly increased the tissue cGMP level, which was significantly decreased in the presence of ODQ. On the other hand, NG‐monomethyl‐l‐arginine (100 μm), a nitric oxide synthase inhibitor, did not inhibit either the negative inotropic effect or cGMP production induced by nifedipine. These results indicate that in rat left ventricular papillary muscle, nifedipine augments its negative inotropic effect at least partly through direct activation of cardiac soluble guanylyl cyclase but not nitric oxide synthase.