Article

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 347, Issue 5, pp 553-561

Relationship between myoglobin contents and increases in cyclic GMP produced by glyceryl trinitrate and nitric oxide in rabbit aorta, right atrium and papillary muscle

  • Takaharu IshibashiAffiliated withDepartment of Pharmacology, Niigata University School of Medicine
  • , Masami HamaguchiAffiliated withDepartment of Pharmacology, Niigata University School of Medicine
  • , Kiminori KatoAffiliated withDepartment of Pharmacology, Niigata University School of Medicine
  • , Tomie KawadaAffiliated withDepartment of Pharmacology, Niigata University School of Medicine
  • , Hideo OhtaAffiliated withDepartment of Pharmacology, Niigata University School of Medicine
  • , Hiroki SasageAffiliated withDepartment of Pharmacology, Niigata University School of Medicine
  • , Shoichi ImaiAffiliated withDepartment of Pharmacology, Niigata University School of Medicine

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Summary

Effects of glyceryl trinitrate (GTN) and nitric oxide (NO) on the cardiac functions and myocardial cyclic GMP (cGMP) contents were examined in comparison with those in the aorta and correlated with myoglobin (an inhibitor of soluble guanylate cyclase) contents using the preparations isolated from the reserpinized rabbit.

GTN (10−10-10−4mol/l) produced a dose-dependent relaxation in the aorta. However, this compound exerted no effect on the rate of the spontaneous beat of the right atrium and the contraction of the papillary muscle. A transient and significant increase in cGMP was observed in the aorta with GTN (3 × 10−6 mol/l). Although the increase was also observed in the right atrium, it was much smaller. No definite change was observed in papillary muscle. Increases in cGMP produced by NO (3 × 10−6 mol/l) were larger and significant in all tissues; (AUCcGMP(GTN)/AUCcGMP(NO)) ratio was 30.1 for the aorta, 65.0 for the right atrium and 16.3% for the papillary muscle. Although higher concentrations of NO were necessary in the right atrium and papillary muscle to induce increases in cGMP, no differences were noted in the three tissues as regards the maximum accumulation of this substance. Furthermore, kinetic analysis of NO-induced increases in tissue cGMP indicated no marked difference in the production rate among the three tissues, while the rate of elimination of cGMP was lower in the aorta than in the atrium or the papillary muscle. The increases in cGMP observed in these three tissues were inversely related to the contents of myoglobin in respective tissues. No effect on myocardial function was observed with NO up to the concentration of 3 × 10−5 mol/l.

These results suggest that myoglobin, an endogenous inhibitor of activation of soluble guanylate cyclase by NO, was responsible for the lower production of cGMP by NO and GTN in the myocardial tissue.

Key words

Glyceryl trinitrate Nitric oxide Cyclic GMP Myoglobin Rabbit myocardium