Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Negative metabolic effects of cyclic GMP in quiescent cardiomyocytes are not related to L-type calcium channel activity


We tested the hypothesis that the negative metabolic effects of elevating cyclic GMP act through inhibition of L-type calcium channels in quiescent cardiac myocytes. The steady state O2 consumption (VO2) of ventricular myocytes, isolated from hearts of New Zealand white rabbits, was measured in a glass chamber using Clark-type oxygen electrodes. The cellular cyclic GMP levels were determined by radioimmunoassay at baseline with either 0.5 mM or 2.0 mM of Ca2+, sodium nitroprusside at increasing concentration (10−8, −6, −4 M) with and without pretreatment by BAY K8644 10−5 M (L-type Ca2+ channel activator) in 0.5 mM Ca2+, or nitroprusside with and without pretreatment with nifedipine 10−4 M (L-type Ca2+ channel blocker) in 2.0 mM Ca2+. In the 0.5 mM Ca2+ medium, basal VO2 was 459±104 (nl O2/min per 105 myocytes) with a corresponding cyclic GMP level of 112±23 (fmol/105 myocytes). With nitroprusside 10−4 M, VO2 was decreased to 285±39 and cyclic GMP level was significantly elevated to 425±128. In the same medium, VO2 was slightly increased by BAY K8644 10−5 M while the cyclic GMP level did not change. With BAY K8644 10−5 M, nitroprusside 10−4 M decreased VO2 and increased cyclic GMP to a level which was similar to cells treated with nitroprusside alone. In the 2.0 mM Ca2+ medium, the basal VO2 and cyclic GMP were 518±121 and 137±24. In the presence of nitroprusside 10−4 M, VO2 was decreased to 295±49 and cyclic GMP was increased to 454±116. In the same medium, nifedipine 10−4 M significantly decreased VO2, while the cyclic GMP level was comparable to the baseline. After nifedipine 10−4 M, nitroprusside 10−4 M decreased VO2 and increased cyclic GMP to levels which were similar to control. Therefore, in quiescent cardiac myocytes, the negative metabolic effects associated with cyclic GMP were not primarily mediated through inhibition of L-type Ca2+ channels.

This is a preview of subscription content, log in to check access.


  1. 1.

    Cornell TL, Arnold E, Boerth NJ, Lincoln TM (1994) Inhibition of smooth muscle growth by nitric oxide and activation of cAMP-dependent protein kinase by cGMP. Am J Physiol 267:C1405–C1413

  2. 2.

    Fischmeister R, Hartzell HC (1987) Cyclic guanosine-3′,5′-monophosphate regulates the calcium current in single cells from frog ventricle. J Physiol (Lond) 387:453–472

  3. 3.

    Fralix TA, Heineman FW, Balaban RS (1991) Effect of work on intracellular calcium of the intact heart. Am J Physiol 261 [Suppl 4]:54–59

  4. 4.

    Gong GX, Weiss HR, Tse J, Scholz PM (1997) Cyclic GMP decreases cardiac myocyte oxygen consumption to a greater extent under conditions of increased metabolism. J Cardiovasc Pharmacol 30:537–543

  5. 5.

    Hartzell HC, Fischmeister R (1986) Opposite effects of cyclic GMP and cyclic AMP on Ca2+ current in single heart cells. Nature 323:273–275

  6. 6.

    Kristein M, Rivet-Bastide M, Hatem S, Benardeau A, Mercadier JJ, Fischmeister R (1995) Nitric oxide regulates the calcium current in isolated human atrial myocytes. J Clin Invest 95:794–802

  7. 7.

    Leone R, Naim KL, Scholz PM, Weiss HR (1998) Increased O2 consumption and positive inotropy caused by cyclic GMP reduction are not altered by L-type calcium channel blockade. Pharmacology 56:37–45

  8. 8.

    Lohmann SM, Fischmeister R, Walter U (1991) Signal transduction by cGMP in heart. Basic Res Cardiol 86:503–514

  9. 9.

    Matsumoto S (1997) Effect of molsidomine on basal Ca2+ current in rat cardiac cells. Life Sci 60:383–390

  10. 10.

    Mery PF, Lohmann SM, Walter U, Fischmeister R (1991) Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes. Proc Natl Acad Sci 88:1197–1201

  11. 11.

    Mery PF, Pavoine C, Belhassen L, Pecker F, Fischmeister R (1993) Nitric oxide regulates cardiac Ca2+ current. Involvement of cGMP-inhibited and cGMP-stimulated phosphodiesterases through guanylyl cyclase activation. J Biol Chem 268:26286–26295

  12. 12.

    Moreno-Sanchez R, Hansford RG (1998) Relation between cytosolic free calcium and respiratory rates in cardiac myocytes. Am J Physiol 255:H347–H357

  13. 13.

    Murad F (1994) The nitric oxide-cGMP signal transduction system for intracellular and intracellular communication. Rec Prog Hormone Res 49:239–248

  14. 14.

    Ono K, Trautwein W (1991) Potentiation by cyclic GMP of beta-adrenergic effect on Ca2+ current in guinea-pig ventricular cells. J Physiol (Lond.) 443:387–404

  15. 15.

    Paulus WJ, Vantrimpont PJ, Shah AM (1994) Acute effects of nitric oxide on left ventricular relaxation and diastolic distensibility in humans. Circulation 89:2070–2078

  16. 16.

    Rose H, Schnitzler N, Kammermeier H (1987) Electrically stimulated cardiomyocytes:evaluation of shortening, oxygen consumption and tracer uptake. Biomed Biochim Acta 8:622–627

  17. 17.

    Rumsey WL, Schlosser C, Nuutinen EM, Robiolio M, Wilson D (1990) Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J Biol Chem 256:15392–15402

  18. 18.

    Schmidt HHHW, Lohmann SM, Walter U (1993) The nitric oxide and cGMP signal transduction system:regulation and mechanism of action. Biochim Biophys Acta 1178:153–175

  19. 19.

    Shah AM, Spurgeon HA, Sollott SJ, Talo A, Lakatta EG (1994) 8-bromo-cGMP reduces the myofilament response to Ca2+ in intact cardiac myocytes. Circ Res 74:970–978

  20. 20.

    Sperelakis N (1994) Regulation of calcium slow channels of heart by cyclic nucleotides and effects of ischemia. Adv Pharmacol 31:1–24

  21. 21.

    Sperelakis N, Tohse N, Ohya Y, Masuda H (1994) Cyclic GMP regulation of calcium slow channels in cardiac muscle and vascular smooth muscle cells. Adv Pharmacol 26:217–252

  22. 22.

    Straznicka M, Gong G, Tse J, Scholz, PM, Weiss HR (1997) The cyclic GMP level which reduces cardiac myocyte O2 consumption is altered in renal hypertension. Am J Physiol 273:H1949–H1955

  23. 23.

    Sumii K, Sperelakis N (1995) cGMP-dependent protein kinase regulation of the L-type Ca2 current in rat ventricular myocytes. Circ Res 77:803–812

  24. 24.

    Tohse N, Nakaya H, Takeda Y, Kanno M (1995) Cyclic GMP-mediated inhibition of L-type Ca2+ channel activity by human natriuretic peptide in rabbit heart cells. Br J Pharmacol 114:1076–1082

  25. 25.

    Weiss HR, Rodriguez E, Tse J, Scholz PM (1994) Effect of increased myocardial cyclic GMP induced by cyclic GMP-phosphodiesterase inhibition on oxygen consumption and supply of rabbit hearts. Clin Exp Pharmacol Physiol 21:607–614

  26. 26.

    Weyrich AS, Ma X, Buerke M, Murohara T, Armstead VE, Lefer AM, Nicholas JM, Lefer DJ, Vinten-Johansen J (1994) Physiological concentrations of nitric oxide do not elicit an acute negative inotropic effect in unstimulated cardiac muscle. Circ Res 75:692–700

  27. 27.

    Wittenberg BA, Robinson TF (1981) Oxygen requirements, morphology, cell coat and membrane permeability of calcium-tolerant myocytes from hearts of adult rats. Cell Tissue Res 216:231–251

Download references

Author information

Correspondence to Harvey R. Weiss.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yan, L., Gong, G.X., Scholz, P.M. et al. Negative metabolic effects of cyclic GMP in quiescent cardiomyocytes are not related to L-type calcium channel activity. Res. Exp. Med. 198, 123–132 (1998).

Download citation

Key words

  • Cardiac myocytes
  • L-type calcium channels
  • Cyclic GMP
  • Nitric oxide
  • Myocyte oxygen consumption