George W J, Busuttil R W, Paddock R J, White L A, Ignarro L J
Recent Adv Stud Cardiac Struct Metab. 1975;8:243-50.
The effects of acetylcholine chloride (ACh) and isoproterenol (Iso) on myocardial levels of guanosine 3', 5'-monophosphate (cyclic GMP) and adenosine 3', 5'-monophosphate (cyclic AMP) and on force of contraction were studied in elelctrically driven isolated rabbit atria. Incubation of atria with Tyrode's solution containing ACh (5 x 10(-7) M) produced significant decreases in contractile force that were associated with significant elevations in atrial cyclic GMP levels. Atrial levels of cyclic AMP were significantly lowered at 15 sec after the addition of ACh but were only slightly lowered at earlier time intervals. The effects of acetylcholine on force of contraction and on cyclic nucleotide levels were prevented with atropine (1 x 10(-7) M). The addition of Iso (1 x 10(-7)-M) to isolated atria produced significant increases in contractile force that were associated with significant elevations in effects of Iso on force of contraction and on cyclic nucleotide levels were prevented with practolol (1 x 10(-5) M). The increases in atrial cyclic GMP and cyclic AMP levels following addition of ACh and Iso, respectively, precede the changes in contractile force. These data support our hypothesis that cyclic AMP and cyclic GMP exert oppositional effects on cardiac contrctility.
在电驱动的离体兔心房中，研究了氯化乙酰胆碱（ACh）和异丙肾上腺素（Iso）对心肌鸟苷3'，5'-单磷酸（环磷酸鸟苷，cyclic GMP）和腺苷3'，5'-单磷酸（环磷酸腺苷，cyclic AMP）水平以及收缩力的影响。用含ACh（5×10⁻⁷M）的台氏液孵育心房，可使收缩力显著降低，这与心房环磷酸鸟苷水平的显著升高相关。加入ACh后15秒，心房环磷酸腺苷水平显著降低，但在较早的时间间隔仅略有降低。阿托品（1×10⁻⁷M）可阻断乙酰胆碱对收缩力和环核苷酸水平的影响。向离体心房加入Iso（1×10⁻⁷M）可使收缩力显著增加，这与环磷酸鸟苷水平的显著升高相关。心得宁（1×10⁻⁵M）可阻断Iso对收缩力和环核苷酸水平的影响。加入ACh和Iso后，心房环磷酸鸟苷和环磷酸腺苷水平的升高分别先于收缩力的变化。这些数据支持我们的假说，即环磷酸腺苷和环磷酸鸟苷对心肌收缩性发挥相反的作用。
