Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1981 Mar;67(3):893–902. doi: 10.1172/JCI110107

Pulmonary Vasodilator Responses to Nitroprusside and Nitroglycerin in the Dog

Philip J Kadowitz 1,2, Premanand Nandiwada 1,2, Carl A Gruetter 1,2, Louis J Ignarro 1,2, Albert L Hyman 1,2
PMCID: PMC370641  PMID: 6782123

Abstract

The objective of this study was to determine the direct actions of nitroprusside and nitroglycerin on the pulmonary vascular bed in the intactchest dog. These widely used nitrogen oxide-containing vasodilator agents decreased pulmonary arterial pressure and increased cardiac output without altering left atrial pressure. Reductions in pulmonary arterial pressure and pulmonary vascular resistance were small under resting conditions, but were enhanced when pulmonary vascular tone was elevated by infusion of a stable prostaglandin analog that increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In studies in which pulmonary blood flow to the left lower lobe was maintained constant, nitroprusside and nitroglycerin caused small but significant reductions in lobar arterial and small-vein pressures without significantly affecting left atrial pressure. With constant blood flow, lobar vascular pressures that were reduced in response to the vasodilators were more greatly reduced when lobar vascular resistance was increased by infusion of the prostaglandin analog or serotonin. However, when lobar vascular pressures were elevated by passive obstruction of lobar venous outflow, vasodilator responses to nitroprusside and nitroglycerin were not enhanced. These data suggest that nitroprusside and nitroglycerin decrease pulmonary vascular resistance by dilating intrapulmonary veins and upstream segments. These responses were minimal under control conditions but were enhanced when vascular tone was increased. This vasodilator action is independent of passive factors such as changes in pulmonary blood flow or left atrial pressure and is not secondary to an effect of these agents on the systemic circulation. Pulmonary vasodilator responses to nitroprusside and nitroglycerin were, however, found to be dependent on the existing level of vasomotor tone in the pulmonary vascular bed.

Full text

PDF
893

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Daoud F. S., Reeves J. T., Kelly D. B. Isoproterenol as a potential pulmonary vasodilator in primary pulmonary hypertension. Am J Cardiol. 1978 Nov;42(5):817–822. doi: 10.1016/0002-9149(78)90102-9. [DOI] [PubMed] [Google Scholar]
  2. Forrester J. S., Ganz W., Diamond G., McHugh T., Chonette D. W., Swan H. J. Thermodilution cardiac output determination with a single flow-directed catheter. Am Heart J. 1972 Mar;83(3):306–311. doi: 10.1016/0002-8703(72)90429-2. [DOI] [PubMed] [Google Scholar]
  3. Fowler N. O., Holmes J. C. Pulmonary arterial pressure at high pulmonary flow. J Clin Invest. 1965 Dec;44(12):2040–2050. doi: 10.1172/JCI105311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. GROVER R. F., REEVES J. T., BLOUNT S. G., Jr Tolazoline hydrochloride (Priscoline): an effective pulmonary vasodilator. Am Heart J. 1961 Jan;61:5–15. doi: 10.1016/0002-8703(61)90510-5. [DOI] [PubMed] [Google Scholar]
  5. Goldstein R. E., Epstein S. E. Editorial: Nitrates in the prophylactic treatment of angina pectoris. Circulation. 1973 Nov;48(5):917–920. doi: 10.1161/01.cir.48.5.917. [DOI] [PubMed] [Google Scholar]
  6. Greenway C. V. Effects of sodium nitroprusside, isosorbide dinitrate, isoproterenol, phentolamine and prazosin on hepatic venous responses to sympathetic nerve stimulation in the cat. J Pharmacol Exp Ther. 1979 Apr;209(1):56–61. [PubMed] [Google Scholar]
  7. Gruetter C. A., Barry B. K., McNamara D. B., Gruetter D. Y., Kadowitz P. J., Ignarro L. Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoamine. J Cyclic Nucleotide Res. 1979;5(3):211–224. [PubMed] [Google Scholar]
  8. Guiha N. H., Cohn J. N., Mikulic E., Franciosa J. A., Limas C. J. Treatment of refractory heart failure with infusion of nitroprusside. N Engl J Med. 1974 Sep 19;291(12):587–592. doi: 10.1056/NEJM197409192911201. [DOI] [PubMed] [Google Scholar]
  9. Hyman A. L., Chapnick B. M., Kadowitz P. J., Lands W. E., Crawford C. G., Fried J., Barton J. Unusual pulmonary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: comparison with endoperoxides and other prostanoids. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5711–5715. doi: 10.1073/pnas.74.12.5711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hyman A. L. Effects of large increases in pulmonary blood flow on pulmonary venous pressure. J Appl Physiol. 1969 Aug;27(2):179–185. doi: 10.1152/jappl.1969.27.2.179. [DOI] [PubMed] [Google Scholar]
  11. Hyman A. L., Kadowitz P. J. Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat. Circ Res. 1979 Sep;45(3):404–409. doi: 10.1161/01.res.45.3.404. [DOI] [PubMed] [Google Scholar]
  12. Hyman A. L., Kadowitz P. J. Vasodilator actions of prostaglandin 6-keto-E1 in the pulmonary vascular bed. J Pharmacol Exp Ther. 1980 Jun;213(3):468–472. [PubMed] [Google Scholar]
  13. Kadowitz P. J., Chapnick B. M., Feigen L. P., Hyman A. L., Nelson P. K., Spannhake E. W. Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin, PGI2. J Appl Physiol Respir Environ Exerc Physiol. 1978 Sep;45(3):408–413. doi: 10.1152/jappl.1978.45.3.408. [DOI] [PubMed] [Google Scholar]
  14. Kadowitz P. J., Hyman A. L. Influence of a prostaglandin endoperoxide analogue on the canine pulmonary vascular bed. Circ Res. 1977 Mar;40(3):282–287. doi: 10.1161/01.res.40.3.282. [DOI] [PubMed] [Google Scholar]
  15. Kadowitz P. J., Joiner P. D., Hyman A. L. Influence of sympathetic stimulation and vasoactive substances on the canine pulmonary veins. J Clin Invest. 1975 Aug;56(2):354–365. doi: 10.1172/JCI108100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kukovetz W. R., Holzmann S., Wurm A., Pöch G. Evidence for cyclic GMP-mediated relaxant effects of nitro-compounds in coronary smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1979 Dec;310(2):129–138. doi: 10.1007/BF00500277. [DOI] [PubMed] [Google Scholar]
  17. Mikulic E., Franciosa J. A., Cohn J. N. Comparative hemodynamic effects of chewable isosorbide dinitrate and nitroglycerin in patients with congestive heart failure. Circulation. 1975 Sep;52(3):477–482. doi: 10.1161/01.cir.52.3.477. [DOI] [PubMed] [Google Scholar]
  18. Mookherjee S., Fuleihan D., Warner R. A., Vardan S., Obeid A. I. Effects of sublingual nitroglycerin on resting pulmonary gas exchange and hemodynamics in man. Circulation. 1978 Jan;57(1):106–110. doi: 10.1161/01.cir.57.1.106. [DOI] [PubMed] [Google Scholar]
  19. Mookherjee S., Keighley J. F., Warner R. A., Bowser M. A., Obeid A. I. Hemodynamic, ventilatory and blood gas changes during infusion of sodium nitroferricyanide (nitroprusside). Studies in patients with congestive heart failure. Chest. 1977 Sep;72(3):273–278. doi: 10.1378/chest.72.3.273. [DOI] [PubMed] [Google Scholar]
  20. Napoli S. A., Gruetter C. A., Ignarro L. J., Kadowitz P. J. Relaxation of bovine coronary arterial smooth muscle by cyclic GMP, cyclic AMP and analogs. J Pharmacol Exp Ther. 1980 Mar;212(3):469–473. [PubMed] [Google Scholar]
  21. Needleman P., Jakschik B., Johnson E. M., Jr Sulfhydryl requirement for relaxation of vascular smooth muscle. J Pharmacol Exp Ther. 1973 Nov;187(2):324–331. [PubMed] [Google Scholar]
  22. Needleman P., Johnson E. M., Jr Mechanism of tolerance development to organic nitrates. J Pharmacol Exp Ther. 1973 Mar;184(3):709–715. [PubMed] [Google Scholar]
  23. Pagani M., Vatner S. F., Braunwald E. Hemodynamic effects of intravenous sodium nitroprusside in the conscious dog. Circulation. 1978 Jan;57(1):144–151. doi: 10.1161/01.cir.57.1.144. [DOI] [PubMed] [Google Scholar]
  24. Palmer R. F., Lasseter K. C. Drug therapy. Sodium nitroprusside. N Engl J Med. 1975 Feb 6;292(6):294–297. doi: 10.1056/NEJM197502062920606. [DOI] [PubMed] [Google Scholar]
  25. Pierpont G., Hale K. A., Franciosa J. A., Cohn J. N. Effects of vasodilators on pulmonary hemodynamics and gas exchange in left ventricular failure. Am Heart J. 1980 Feb;99(2):208–216. doi: 10.1016/0002-8703(80)90767-x. [DOI] [PubMed] [Google Scholar]
  26. Rubin L. J., Peter R. H. Oral hydralazine therapy for primary pulmonary hypertension. N Engl J Med. 1980 Jan 10;302(2):69–73. doi: 10.1056/NEJM198001103020201. [DOI] [PubMed] [Google Scholar]
  27. Rubin S. A., Misbach G., Lekven J., Parmley W. W., Tyberg J. V. Resistance and volume changes caused by nitroprusside in the dog. Am J Physiol. 1979 Jul;237(1):H99–103. doi: 10.1152/ajpheart.1979.237.1.H99. [DOI] [PubMed] [Google Scholar]
  28. Ruskin J. N., Hutter A. M., Jr Primary pulmonary hypertension treated with oral phentolamine. Ann Intern Med. 1979 May;90(5):772–774. doi: 10.7326/0003-4819-90-5-772. [DOI] [PubMed] [Google Scholar]
  29. Sivak E. D., Gray B. A., McCurdy H. T., Phillips A. K. Pulmonary vascular response to nitroprusside in dogs. Circ Res. 1979 Sep;45(3):360–365. doi: 10.1161/01.res.45.3.360. [DOI] [PubMed] [Google Scholar]
  30. Vatner S. F., Pagani M., Rutherford J. D., Millard R. W., Manders W. T. Effects of nitroglycerin on cardiac function and regional blood flow distribution in conscious dogs. Am J Physiol. 1978 Mar;234(3):H244–H252. doi: 10.1152/ajpheart.1978.234.3.H244. [DOI] [PubMed] [Google Scholar]
  31. Wang S. W., Pohl J. E., Rowlands D. J., Wade E. G. Diazoxide in treatment of primary pulmonary hypertension. Br Heart J. 1978 May;40(5):572–574. doi: 10.1136/hrt.40.5.572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Watkins W. D., Peterson M. B., Crone R. K., Shannon D. C., Levine L. Prostacyclin and prostaglandin E1 for severe idiopathic pulmonary artery hypertension. Lancet. 1980 May 17;1(8177):1083–1083. doi: 10.1016/s0140-6736(80)91522-6. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES