Hui J, Tabatabaei A, MacLeod K M
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Cardiovasc Res. 1995 Sep;30(3):372-6.
The purpose of the present investigation was to determine whether stimulation of the nitric oxide synthase pathway contributes to the muscarinic receptor-mediated elevation in cGMP levels and reversal of the positive inotropic response to the adenylyl cyclase activator forskolin in rabbit papillary muscles.
Intact rabbit papillary muscles suspended under tension in isolated tissue baths were incubated in the absence or presence of the nitric oxide synthase inhibitor L-NG-monomethyl arginine (L-NMMA) and then treated with forskolin followed by the muscarinic agonist carbachol. The developed tension of the preparations was monitored during their exposure to drug. Papillary muscles were then frozen and subsequently assayed for cGMP levels by radioimmunoassay. Tension and cGMP levels were also measured in some papillary muscles treated with forskolin followed by sodium nitroprusside.
Incubation of papillary muscles with L-NMMA completely blocked increases in cGMP levels produced by carbachol, but had no effect on the reversal by carbachol of the increase in tension in response to forskolin. Sodium nitroprusside also caused a marked elevation of cGMP levels in rabbit papillary muscle, but had no significant effect on the forskolin-induced increase in tension.
These data demonstrate that activation of muscarinic receptors results in increases in cGMP levels largely through the nitric oxide synthase pathway in rabbit papillary muscles. However, the cGMP produced through this pathway or by sodium nitroprusside does not appear to contribute to the reversal of the positive inotropic response to forskolin.
本研究的目的是确定一氧化氮合酶途径的激活是否有助于毒蕈碱受体介导的兔乳头肌中环鸟苷酸（cGMP）水平升高以及对腺苷酸环化酶激活剂福斯高林的正性肌力反应的逆转。
将在离体组织浴中受张力悬挂的完整兔乳头肌在不存在或存在一氧化氮合酶抑制剂L-NG-单甲基精氨酸（L-NMMA）的情况下孵育，然后用福斯高林处理，随后用毒蕈碱激动剂卡巴胆碱处理。在制剂暴露于药物期间监测其产生的张力。然后将乳头肌冷冻，随后通过放射免疫测定法测定cGMP水平。还用福斯高林处理后再用硝普钠处理的一些乳头肌测量张力和cGMP水平。
用L-NMMA孵育乳头肌完全阻断了卡巴胆碱产生的cGMP水平升高，但对卡巴胆碱逆转福斯高林引起的张力增加没有影响。硝普钠也使兔乳头肌中的cGMP水平显著升高，但对福斯高林引起的张力增加没有显著影响。
这些数据表明，在兔乳头肌中，毒蕈碱受体的激活主要通过一氧化氮合酶途径导致cGMP水平升高。然而，通过该途径或硝普钠产生的cGMP似乎对福斯高林的正性肌力反应的逆转没有作用。
