Shan Q, Bourreau J
Department of Physiology, Institute of Cardiovascular Sciences and Medicine, The University of Hong Kong, 5 Sassoon Road, SAR, Hong Kong, People's Republic of China.
Eur J Pharmacol. 2000 Oct 13;406(2):257-64. doi: 10.1016/s0014-2999(00)00660-9.
In the present study, intraperitoneal injection of lipopolysaccharide (10 mg/kg) to anaesthetized rats produced a gradual fall in mean arterial pressure in 6 h. Aortic rings from lipopolysaccharide-treated rats showed a significant reduction in the contractile response to vasoconstrictors. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) or aminoguanidine, two nitric oxide synthase (NOS) inhibitors, abolished this vascular hyporeactivity. In ventricular myocytes isolated from lipopolysaccharide-treated rats, both electrically induced Ca(2+) transients and the intracellular Ca(2+) response to beta-adrenergic stimulation were significantly depressed when compared with those recorded from myocytes from sham control rats. L-NAME and aminoguanidine alone had no effects on electrically stimulated Ca(2+) transients in ventricular myocytes either from control or lipopolysaccharide-treated rats. However, these two NOS inhibitors augmented the intracellular Ca(2+) response to beta-adrenergic stimulation in myocytes from lipopolysaccharide-treated rats, but not in control myocytes. In addition, 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ), an inhibitor of nitric oxide (NO)-sensitive guanylyl cyclase, also reversed the intracellular Ca(2+) hyporesponsiveness to beta-adrenergic stimulation in myocytes from lipopolysaccharide-treated rats. In cardiac myocytes from lipopolysaccharide-rats pretreated with aminoguanidine, the intracellular Ca(2+) hyporesponsiveness to beta-adrenergic stimulation was abolished. However, there still existed a depressed Ca(2+) response to electrical field stimulation. These data indicate that NO following lipopolysaccharide stimulation contributes to vascular hyporeactivity and the depressed intracellular Ca(2+) response to beta-adrenergic stimulation in lipopolysaccharide-treated rats, but is not responsible for the reduced Ca(2+) response to electrical stimulation in our experimental conditions.
在本研究中，给麻醉大鼠腹腔注射脂多糖（10毫克/千克），6小时内平均动脉压逐渐下降。脂多糖处理大鼠的主动脉环对血管收缩剂的收缩反应显著降低。用两种一氧化氮合酶（NOS）抑制剂N（G）-硝基-L-精氨酸甲酯（L-NAME）或氨基胍预处理可消除这种血管反应性低下。与假手术对照大鼠的心肌细胞相比，从脂多糖处理大鼠分离的心室肌细胞中，电诱导的Ca（2+）瞬变和细胞内Ca（2+）对β-肾上腺素能刺激的反应均显著降低。单独使用L-NAME和氨基胍对对照或脂多糖处理大鼠的心室肌细胞电刺激的Ca（2+）瞬变均无影响。然而，这两种NOS抑制剂增强了脂多糖处理大鼠心肌细胞对β-肾上腺素能刺激的细胞内Ca（2+）反应，但对对照心肌细胞无此作用。此外，一氧化氮（NO）敏感型鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ）也逆转了脂多糖处理大鼠心肌细胞对β-肾上腺素能刺激的细胞内Ca（2+）低反应性。在用氨基胍预处理的脂多糖大鼠的心肌细胞中，对β-肾上腺素能刺激的细胞内Ca（2+）低反应性被消除。然而，对电场刺激的Ca（2+）反应仍存在降低。这些数据表明，脂多糖刺激后产生的NO导致脂多糖处理大鼠的血管反应性低下和细胞内Ca（2+）对β-肾上腺素能刺激的反应降低，但在我们的实验条件下，对电场刺激的Ca（2+）反应降低并无责任。
