Summary
Dibutyryl cyclic GMP was given intravenously to anesthetized dogs with doses of 0.0625. 0.125, 0.25, 0.5 and 1.0 mg/kg, respectively. It induced decreases in blood pressure, heart rate, max LV dp/dt and total peripheral resistance with increase of stroke volume in a dose-dependent manner. Although these effects began to appear 30 sec after the administration in each dose, the duration of the effect was oberved 50 sec after the administration. Effects of 1 mg/kg dibutyryl cyclic GMP on mean blood pressure and max LV dp/dt were almost equal to those of 3 μg/kg acetylcholine, but dibutyryl cyclic GMP was revealed to have a slower onset and longer acting effects than acetylcholine. The administration of atropine did not block the effect of dibutyryl cyclic GMP but blocked those of acetylcholine. These results indicate that dibutyryl cyclic GMP does not exert these effects through muscarinic receptors in spite of its acetylcholine-like effects.
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References
Andersson R, Nilsson K, Wikberg J, Johansson S, Lundholm EM, Lundholm L (1975) Cyclic nucleotides and the contraction of smooth muscle. Adv Cyclic Nucleotide Res 5:491–518
Ashman DF, Lipton R, Melicow MM, Price TD (1963) Isolation of adenosine 3′, 5′-monophosphate and guanosine 3′, 5′-monophosphate from rat urine. Biochem Biophys Res Commun 11:330–334
George WJ, Polson JB, O'Toole AG, Goldberg ND (1970) Elevation of guanosine 3′, 5′-cyclic phosphate in rat heart after perfusion with acetylcholine. Proc Nat Acad Sci 66:398–403
Hashimoto H, Okumura K, Niizoe K, Ogawa K (1982) Effects of dibutyryl cyclic AMP in patients with severe heart failure. Jpn Heart J 23:1021–1027
Higgins CB, Vatner SF, Braunwald E (1973) Parasympathetic control of the heart. Pharmacol Rev 25:119–155
Ishikawa E, Ishikawa S, Davis JW, Sutherland EW (1969) Determination of guanosine 3′, 5′-monophosphate in tissues and of guanyl cyclase in rat intestine. J Biol Chem 244:6371–6376
Keith RA, Burkman AM, Sokoloski TD, Fertel RH (1982) Vascular tolerance to nitroglycerin and cyclic GMP generation in rat aortic smooth muscle. J Pharmacol Exp Ther 221:525–531
Kuo JF, Lee TP, Reyes PL, Walton KG, Donnelly TE Jr, Greengard P (1972) Cyclic nucleotide-dependent protein kinases. An assay method for the measurement of guanosine 3′, 5′-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J Biol Chem 247:16–22
Lee TP, Kuo JF, Greengard P (1972) Role of muscarinic cholinergic receptors in regulation of guanosine 3′, 5′-cyclic monophosphate content in mammalian brain, heart muscle and intestinal smooth muscle. Proc Nat Acad Sci USA 69:3287–3291
Nawrath H (1976) Cyclic AMP and cyclic GMP may play opposing roles in influencing force of contraction in mammalian myocardium. Nature 262:509–511
Nawrath H (1977) Does cyclic GMP mediate the negative inotropic effect of acetylcholine in the heart. Nature 267:73–74
Schwegler M, Jacob R (1976) Catecholamine antagonism of acetylcholine and dibutyryl guanosine 3′, 5′-monophosphate in the mammalian ventricular myocardium. IV. Annual meeting of the international study group for research in cardiac metabolism 1973. In: Recent advances in studies on cardiac structure and metabolism, Vol 7, p 391–399
Schwegler M, Reutter K, Sieber G, Jacob R (1976) Noncompetitive catecholamine-antagonism of acetylcholine in the sympathectomized mammalian ventricular myocardium. Basic Res Cardiol 71:407–419
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Imura, K., Ogawa, K. & Satake, T. Hemodynamic effects of dibutyryl cyclic GMP in anesthetized dogs. Basic Res Cardiol 81, 276–282 (1986). https://doi.org/10.1007/BF01907410
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DOI: https://doi.org/10.1007/BF01907410