Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Sep;104(1):7–14. doi: 10.1111/j.1476-5381.1991.tb12376.x

Cardiovascular profile of 5 novel nitrate-esters: a comparative study with nitroglycerin in pigs with and without left ventricular dysfunction.

L J van Woerkens 1, W J van der Giessen 1, P D Verdouw 1
PMCID: PMC1908261  PMID: 1786521

Abstract

1. Four cumulative 10 min intravenous infusions of 0.05, 0.2, 0.5 and 2.0 mg min-1 were used to compare the cardiovascular profile of 5 novel nitrate-esters dissolved in Intralipid 10% to that of nitroglycerin (GTN) in conscious pigs. 2. Infusion of Intralipid 10% alone had no effect on any of the systemic haemodynamic parameters. GTN infusions decreased mean arterial blood pressure dose-dependently from 94 +/- 2 mmHg to 79 +/- 3 mmHg (P less than 0.05) and raised cardiac output from 2.74 +/- 0.09 l min-1 to 3.40 +/- 0.18 l min-1 (P less than 0.05) due to an increase in heart rate (by up to 43 +/- 3%), as stroke volume decreased slightly. Systemic vascular resistance decreased (by 32 +/- 3%) and left ventricular end-diastolic pressure fell from 5.2 +/- 0.4 mmHg to 2.2 +/- 0.5 mmHg (both P less than 0.05). 3. The novel compounds CEDO 8811, CEDO 8834 and CEDO 8901 increased cardiac output only at the highest dose (7%, 8% and 9%, respectively). There was no change in mean arterial blood pressure as the increase in cardiac output was counterbalanced by arterial vasodilatation. All three compounds reduced left ventricular end-diastolic pressure slightly. 4. CEDO 8816 was a more potent arterial and venodilator than the aforementioned CEDO compounds, as the decreases in systemic vascular resistance and left ventricular end-diastolic pressure were already significant at lower doses. The fall in stroke volume was fully compensated by the increase in heart rate and as a result cardiac output increased by 11 +/- 3% (P less than 0.05) at the highest dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
7

Selected References

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

  1. Adachi H., Tomoike H., Nishijima H., Hayashi Y., Yamada A., Nakamura M. Effects of verapamil and nitroglycerin on coronary and systemic hemodynamics in conscious dogs. J Pharmacol Exp Ther. 1987 Jun;241(3):1072–1078. [PubMed] [Google Scholar]
  2. Canty J. M., Jr, Giglia J., Kandath D. Effect of tachycardia on regional function and transmural myocardial perfusion during graded coronary pressure reduction in conscious dogs. Circulation. 1990 Nov;82(5):1815–1825. doi: 10.1161/01.cir.82.5.1815. [DOI] [PubMed] [Google Scholar]
  3. Capurro N. L., Kent K. M., Smith H. J., Aamodt R., Epstein S. E. Acute coronary occlusion: prolonged increase in collateral flow following brief administration of nitroglycerin and methoxamine. Am J Cardiol. 1977 May 4;39(5):679–683. doi: 10.1016/s0002-9149(77)80128-8. [DOI] [PubMed] [Google Scholar]
  4. Colley P. S., Sivarajan M. Regional blood flow in dogs during halothane anesthesia and controlled hypotension produced by nitroprusside or nitroglycerin. Anesth Analg. 1984 May;63(5):503–510. [PubMed] [Google Scholar]
  5. Creager M. A., Massie B. M., Faxon D. P., Friedman S. D., Kramer B. L., Weiner D. A., Ryan T. J., Topic N., Melidossian C. D. Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure. J Am Coll Cardiol. 1985 Jul;6(1):163–173. doi: 10.1016/s0735-1097(85)80269-2. [DOI] [PubMed] [Google Scholar]
  6. Cruickshank J. M., Thorp J. M., Zacharias F. J. Benefits and potential harm of lowering high blood pressure. Lancet. 1987 Mar 14;1(8533):581–584. doi: 10.1016/s0140-6736(87)90231-5. [DOI] [PubMed] [Google Scholar]
  7. Duncker D. J., Saxena P. R., Verdouw P. D. Systemic haemodynamics of dihydropyridine derivatives in conscious pigs with or without propranolol. Eur J Pharmacol. 1988 Nov 8;156(3):401–409. doi: 10.1016/0014-2999(88)90286-5. [DOI] [PubMed] [Google Scholar]
  8. Flaherty J. T. Comparison of intravenous nitroglycerin and sodium nitroprusside in acute myocardial infarction. Am J Med. 1983 Jun 27;74(6B):53–60. doi: 10.1016/0002-9343(83)90855-0. [DOI] [PubMed] [Google Scholar]
  9. Flaherty J. T., Reid P. R., Kelly D. T., Taylor D. R., Weisfeldt M. L., Pitt B. Intravenous nitroglycerin in acute myocardial infarction. Circulation. 1975 Jan;51(1):132–139. doi: 10.1161/01.cir.51.1.132. [DOI] [PubMed] [Google Scholar]
  10. Hoffman J. I. Autoregulation and heart rate. Circulation. 1990 Nov;82(5):1880–1881. doi: 10.1161/01.cir.82.5.1880. [DOI] [PubMed] [Google Scholar]
  11. Leier C. V., Huss P., Magorien R. D., Unverferth D. V. Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure. Circulation. 1983 Apr;67(4):817–822. doi: 10.1161/01.cir.67.4.817. [DOI] [PubMed] [Google Scholar]
  12. Macho P., Vatner S. F. Effects of nitroglycerin and nitroprusside on large and small coronary vessels in conscious dogs. Circulation. 1981 Dec;64(6):1101–1107. doi: 10.1161/01.cir.64.6.1101. [DOI] [PubMed] [Google Scholar]
  13. Mason D. T., Zelis R., Amsterdam E. A. Actions of the nitrites on the peripheral circulation and myocardial oxygen consumption: significance in the relief of angina pectoris. Chest. 1971 Mar;59(3):296–305. doi: 10.1378/chest.59.3.296. [DOI] [PubMed] [Google Scholar]
  14. Most A. S., Williams D. O., Millard R. W. Acute coronary occlusion in the pig: effect of nitroglycerin on regional myocardial blood flow. Am J Cardiol. 1978 Dec;42(6):947–953. doi: 10.1016/0002-9149(78)90680-x. [DOI] [PubMed] [Google Scholar]
  15. Norlén K. Central and regional haemodynamics during controlled hypotension produced by adenosine, sodium nitroprusside and nitroglycerin. Studies in the pig. Br J Anaesth. 1988 Aug;61(2):186–193. doi: 10.1093/bja/61.2.186. [DOI] [PubMed] [Google Scholar]
  16. Packer M. New perspectives on therapeutic application of nitrates as vasodilator agents for severe chronic heart failure. Am J Med. 1983 Jun 27;74(6B):61–72. doi: 10.1016/0002-9343(83)90856-2. [DOI] [PubMed] [Google Scholar]
  17. Verdouw P. D., Hartog J. M., Ruggeman A. M. Systemic and regional myocardial responses to AR-L 115 BS, a positive inotropic imidazo-pyridine, in the absence or in the presence of the bradycardiac action of alinidine. Basic Res Cardiol. 1981 May-Jun;76(3):328–343. doi: 10.1007/BF01907776. [DOI] [PubMed] [Google Scholar]
  18. van der Giessen W. J., Duncker D. J., Saxena P. R., Verdouw P. D. Nimodipine has no effect on the cerebral circulation in conscious pigs, despite an increase in cardiac output. Br J Pharmacol. 1990 Jun;100(2):277–282. doi: 10.1111/j.1476-5381.1990.tb15795.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. van der Giessen W. J., van Woerkens L. J., Duncker D. J., Roelandt J. R., Verdouw P. D. Acute hemodynamic effects of nisoldipine and pimobendan in conscious pigs with chronic heart failure. J Cardiovasc Pharmacol. 1989 Oct;14(4):653–658. doi: 10.1097/00005344-198910000-00019. [DOI] [PubMed] [Google Scholar]
  20. van der Giessen W. J., van Woerkens L. J., Saxena P. R., Roelandt J. R., Verdouw P. D. Nisoldipine improves blood flow to skeletal muscles in conscious pigs with chronic heart failure. Eur Heart J. 1990 Jun;11(6):552–559. doi: 10.1093/oxfordjournals.eurheartj.a059749. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES