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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Jun;118(3):466–470. doi: 10.1111/j.1476-5381.1996.tb15426.x

Relaxation of guinea-pig trachea by sodium nitroprusside: cyclic GMP and nitric oxide not involved.

G Sadeghi-Hashjin 1, G Folkerts 1, P A Henricks 1, P G van de Loo 1, I E Dik 1, F P Nijkamp 1
PMCID: PMC1909714  PMID: 8762066

Abstract

1. Sodium nitroprusside (SNP) completely relaxed the guinea-pig isolated, perfused trachea in a concentration-dependent manner. Although SNP was less potent by about 2 orders of magnitude, its maximal effect was 25% higher compared to isoprenaline. 2. SNP (3.2 microM) increased cyclic GMP levels by 300% and relaxed guinea-pig isolated, perfused trachea by 54%. The SNP-induced relaxations of the preparations were not affected by the guanylate cyclase inhibitor, methylene blue. Moreover, zaprinast, a cyclic GMP-specific phosphodiesterase inhibitor which was supposed to enhance SNP-induced relaxations, decreased the maximal relaxation by 22% (P < 0.001). 3. In contrast, 8Br-cyclic GMP (10 microM) increased the cyclic GMP levels by 1100% without inducing a marked relaxation. 4. SNP (10 microM) and S-nitroso-N-acetylpenicillamine (SNAP; a direct donor of nitric oxide; 10 microM), relaxed the tissues by 75% and 25%, respectively, without any nitric oxide (NO) release by SNP (< 1 pmol 100 microliters-1), but a substantial NO release by SNAP (560 pmol 100 microliters-1). 5. It is concluded that the SNP-induced tracheal relaxations are probably not mediated by cyclic GMP and NO.

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Selected References

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  1. Arnold W. P., Longnecker D. E., Epstein R. M. Photodegradation of sodium nitroprusside: biologic activity and cyanide release. Anesthesiology. 1984 Sep;61(3):254–260. doi: 10.1097/00000542-198409000-00004. [DOI] [PubMed] [Google Scholar]
  2. Axelsson K. L., Andersson R. G., Wikberg J. E. Vascular smooth muscle relaxation by nitro compounds: reduced relaxation and cGMP elevation in tolerant vessels and reversal of tolerance by dithiothreitol. Acta Pharmacol Toxicol (Copenh) 1982 May;50(5):350–357. doi: 10.1111/j.1600-0773.1982.tb00986.x. [DOI] [PubMed] [Google Scholar]
  3. Buga G. M., Gold M. E., Wood K. S., Chaudhuri G., Ignarro L. J. Endothelium-derived nitric oxide relaxes nonvascular smooth muscle. Eur J Pharmacol. 1989 Feb 14;161(1):61–72. doi: 10.1016/0014-2999(89)90180-5. [DOI] [PubMed] [Google Scholar]
  4. Diamond J., Chu E. B. Possible role for cyclic GMP in endothelium-dependent relaxation of rabbit aorta by acetylcholine. Comparison with nitroglycerin. Res Commun Chem Pathol Pharmacol. 1983 Sep;41(3):369–381. [PubMed] [Google Scholar]
  5. Diamond J., Janis R. A. Increases in cyclic GMP levels may not mediate relaxant effects of sodium nitroprusside, verapamil and hydralazine in rat vas deferens. Nature. 1978 Feb 2;271(5644):472–473. doi: 10.1038/271472a0. [DOI] [PubMed] [Google Scholar]
  6. Fedan J. S., Warner T. E., Yuan L. X., Robinson V. a., Frazer D. G. Nitric oxide synthase inhibitor and lipopolysaccharide effects on reactivity of guinea pig airways. J Pharmacol Exp Ther. 1995 Mar;272(3):1141–1150. [PubMed] [Google Scholar]
  7. Folkerts G., van der Linde H. J., Nijkamp F. P. Virus-induced airway hyperresponsiveness in guinea pigs is related to a deficiency in nitric oxide. J Clin Invest. 1995 Jan;95(1):26–30. doi: 10.1172/JCI117649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Folkerts G., van der Linde H., Verheyen A. K., Nijkamp F. P. Endogenous nitric oxide modulation of potassium-induced changes in guinea-pig airway tone. Br J Pharmacol. 1995 Aug;115(7):1194–1198. doi: 10.1111/j.1476-5381.1995.tb15024.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gaston B., Drazen J. M., Jansen A., Sugarbaker D. A., Loscalzo J., Richards W., Stamler J. S. Relaxation of human bronchial smooth muscle by S-nitrosothiols in vitro. J Pharmacol Exp Ther. 1994 Feb;268(2):978–984. [PubMed] [Google Scholar]
  10. Gruetter C. A., Childers C. E., Bosserman M. K., Lemke S. M., Ball J. G., Valentovic M. A. Comparison of relaxation induced by glyceryl trinitrate, isosorbide dinitrate, and sodium nitroprusside in bovine airways. Am Rev Respir Dis. 1989 May;139(5):1192–1197. doi: 10.1164/ajrccm/139.5.1192. [DOI] [PubMed] [Google Scholar]
  11. Ignarro L. J., Edwards J. C., Gruetter D. Y., Barry B. K., Gruetter C. A. Possible involvement of S-nitrosothiols in the activation of guanylate cyclase by nitroso compounds. FEBS Lett. 1980 Feb 11;110(2):275–278. doi: 10.1016/0014-5793(80)80091-3. [DOI] [PubMed] [Google Scholar]
  12. Ignarro L. J., Kadowitz P. J. The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Annu Rev Pharmacol Toxicol. 1985;25:171–191. doi: 10.1146/annurev.pa.25.040185.001131. [DOI] [PubMed] [Google Scholar]
  13. Katsuki S., Murad F. Regulation of adenosine cyclic 3',5'-monophosphate and guanosine cyclic 3',5'-monophosphate levels and contractility in bovine tracheal smooth muscle. Mol Pharmacol. 1977 Mar;13(2):330–341. [PubMed] [Google Scholar]
  14. Kong S. K., Choy Y. M., Lee C. Y. The nitric oxide donor, sodium nitroprusside, increased intranuclear and cytosolic free calcium concentration in single PU5-1.8 cells. Biochem Biophys Res Commun. 1994 Feb 28;199(1):234–240. doi: 10.1006/bbrc.1994.1219. [DOI] [PubMed] [Google Scholar]
  15. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  16. Murad F., Mittal C. K., Arnold W. P., Katsuki S., Kimura H. Guanylate cyclase: activation by azide, nitro compounds, nitric oxide, and hydroxyl radical and inhibition by hemoglobin and myoglobin. Adv Cyclic Nucleotide Res. 1978;9:145–158. [PubMed] [Google Scholar]
  17. Nijkamp F. P., Folkerts G. Nitric oxide and bronchial reactivity. Clin Exp Allergy. 1994 Oct;24(10):905–914. doi: 10.1111/j.1365-2222.1994.tb02721.x. [DOI] [PubMed] [Google Scholar]
  18. Nijkamp F. P., van der Linde H. J., Folkerts G. Nitric oxide synthesis inhibitors induce airway hyperresponsiveness in the guinea pig in vivo and in vitro. Role of the epithelium. Am Rev Respir Dis. 1993 Sep;148(3):727–734. doi: 10.1164/ajrccm/148.3.727. [DOI] [PubMed] [Google Scholar]
  19. Shahid M., van Amsterdam R. G., de Boer J., ten Berge R. E., Nicholson C. D., Zaagsma J. The presence of five cyclic nucleotide phosphodiesterase isoenzyme activities in bovine tracheal smooth muscle and the functional effects of selective inhibitors. Br J Pharmacol. 1991 Oct;104(2):471–477. doi: 10.1111/j.1476-5381.1991.tb12453.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stuart-Smith K., Bynoe T. C., Lindeman K. S., Hirshman C. A. Differential effects of nitrovasodilators and nitric oxide on porcine tracheal and bronchial muscle in vitro. J Appl Physiol (1985) 1994 Sep;77(3):1142–1147. doi: 10.1152/jappl.1994.77.3.1142. [DOI] [PubMed] [Google Scholar]
  21. Stuart-Smith K., Vanhoutte P. M. Epithelium, contractile tone, and responses to relaxing agonists in canine bronchi. J Appl Physiol (1985) 1990 Aug;69(2):678–685. doi: 10.1152/jappl.1990.69.2.678. [DOI] [PubMed] [Google Scholar]
  22. Suzuki K., Takagi K., Satake T., Sugiyama S., Ozawa T. The relationship between tissue levels of cyclic GMP and tracheal smooth muscle relaxation in the guinea-pig. Clin Exp Pharmacol Physiol. 1986 Jan;13(1):39–46. doi: 10.1111/j.1440-1681.1986.tb00313.x. [DOI] [PubMed] [Google Scholar]
  23. Torphy T. J., Zhou H. L., Burman M., Huang L. B. Role of cyclic nucleotide phosphodiesterase isozymes in intact canine trachealis. Mol Pharmacol. 1991 Mar;39(3):376–384. [PubMed] [Google Scholar]
  24. Tremblay J., Gerzer R., Hamet P. Cyclic GMP in cell function. Adv Second Messenger Phosphoprotein Res. 1988;22:319–383. [PubMed] [Google Scholar]
  25. Waldman S. A., Murad F. Cyclic GMP synthesis and function. Pharmacol Rev. 1987 Sep;39(3):163–196. [PubMed] [Google Scholar]
  26. Zhang Y., Palette-Pays C., Naline E., Varoquaux O., Advenier C. Effect of molsidomine and linsidomine on the human isolated bronchus and the guinea-pig isolated trachea. J Pharm Pharmacol. 1993 Apr;45(4):280–285. doi: 10.1111/j.2042-7158.1993.tb05553.x. [DOI] [PubMed] [Google Scholar]
  27. Zhou H. L., Torphy T. J. Relationship between cyclic guanosine monophosphate accumulation and relaxation of canine trachealis induced by nitrovasodilators. J Pharmacol Exp Ther. 1991 Sep;258(3):972–978. [PubMed] [Google Scholar]

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