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. 1995 May;73(5):434–441. doi: 10.1136/hrt.73.5.434

Peripheral haemodynamic effects of inhibition of prostaglandin synthesis in congestive heart failure and interactions with captopril.

J N Townend 1, J Doran 1, C J Lote 1, M K Davies 1
PMCID: PMC483859  PMID: 7786658

Abstract

OBJECTIVES--To investigate the role of prostaglandins in maintaining circulatory homoeostasis in chronic heart failure and the hypothesis that an increase in vasodilatory prostaglandin synthesis may contribute to the actions of angiotensin converting enzyme inhibitors in heart failure. DESIGN--Randomised, double blind, placebo controlled studies. Cardiac output and renal and limb blood flow were measured after oral indomethacin 50 mg or placebo followed by "open" intravenous infusion of prostaglandin E2 (study A). In a second study the same measurements were made after oral indomethacin 50 mg or placebo was given 30 min before "open" captopril (study B). METHODS--Blood pressure was measured using a mercury sphygmomanometer. Cardiac output was determined by Doppler interrogation of blood flow in the ascending aorta and echocardiographic measurement of aortic root diameter. Renal blood flow was calculated from the effective renal plasma flow measured by p-aminohippurate clearance and the haematocrit, and glomerular filtration rate by endogenous creatinine clearance. Limb blood flow was measured by venous occlusion plethysmography using mercury in silastic strain gauges. The concentration of plasma prostaglandin E2 was measured by radioimmunoassay. SETTING--University department of cardiovascular medicine. PATIENTS--12 patients with chronic stable heart failure before starting treatment with angiotensin converting enzyme inhibitors. RESULTS--Indomethacin resulted in adverse effects on cardiac output, systemic vascular resistance, renal blood flow, glomerular filtration, urinary sodium excretion, and calf vascular resistance. Changes were reversed with infusion of prostaglandin E2. Pretreatment with indomethacin resulted in the attenuation of the acute increase in cardiac output and decrease in systemic vascular resistance that occurred with captopril. Similarly, an increase in renal blood flow with captopril was attenuated by indomethacin. CONCLUSIONS--The acute adverse effects of indomethacin on central and peripheral haemodynamic and renal function suggest that prostaglandins have a significant role in the regulation of peripheral blood flow and renal function in patients with stable chronic heart failure. The attenuation by indomethacin of captopril induced improvements in haemodynamic function and renal blood flow is consistent with the hypothesis that captopril may act in part via an increase in prostaglandin synthesis.

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Selected References

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  1. Boyer T. D., Zia P., Reynolds T. B. Effect of indomethacin and prostaglandin A1 on renal function and plasma renin activity in alcoholic liver disease. Gastroenterology. 1979 Aug;77(2):215–222. [PubMed] [Google Scholar]
  2. Chasis H., Redish J., Goldring W., Ranges H. A., Smith H. W. THE USE OF SODIUM p-AMINOHIPPURATE FOR THE FUNCTIONAL EVALUATION OF THE HUMAN KIDNEY. J Clin Invest. 1945 Jul;24(4):583–588. doi: 10.1172/JCI101639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cleland J. G., Dargie H. J., Ball S. G., Gillen G., Hodsman G. P., Morton J. J., East B. W., Robertson I., Ford I., Robertson J. I. Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones, and metabolic state. Br Heart J. 1985 Sep;54(3):305–312. doi: 10.1136/hrt.54.3.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Creager M. A., Halperin J. L., Bernard D. B., Faxon D. P., Melidossian C. D., Gavras H., Ryan T. J. Acute regional circulatory and renal hemodynamic effects of converting-enzyme inhibition in patients with congestive heart failure. Circulation. 1981 Sep;64(3):483–489. doi: 10.1161/01.cir.64.3.483. [DOI] [PubMed] [Google Scholar]
  5. Donker A. J., Arisz L., Brentjens J. R., van der Hem G. K., Hollemans H. J. The effect of indomethacin on kidney function and plasma renin activity in man. Nephron. 1976;17(4):288–296. doi: 10.1159/000180733. [DOI] [PubMed] [Google Scholar]
  6. Dusting G. J., Moncada S., Vane J. R. Prostaglandins, their intermediates and precursors: cardiovascular actions and regulatory roles in normal and abnormal circulatory systems. Prog Cardiovasc Dis. 1979 May-Jun;21(6):405–430. doi: 10.1016/0033-0620(79)90024-0. [DOI] [PubMed] [Google Scholar]
  7. Dzau V. J., Packer M., Lilly L. S., Swartz S. L., Hollenberg N. K., Williams G. H. Prostaglandins in severe congestive heart failure. Relation to activation of the renin--angiotensin system and hyponatremia. N Engl J Med. 1984 Feb 9;310(6):347–352. doi: 10.1056/NEJM198402093100603. [DOI] [PubMed] [Google Scholar]
  8. Dzau V. J., Swartz S. L. Dissociation of the prostaglandin and renin angiotensin systems during captopril therapy for chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol. 1987 Nov 1;60(13):1101–1105. doi: 10.1016/0002-9149(87)90361-4. [DOI] [PubMed] [Google Scholar]
  9. Dzau V. J. Vascular and renal prostaglandins as counter-regulatory systems in heart failure. Eur Heart J. 1988 Jun;9 (Suppl H):15–19. doi: 10.1093/eurheartj/9.suppl_h.15. [DOI] [PubMed] [Google Scholar]
  10. Güllner H. G., Gill J. R., Jr, Bartter F. C., Düsing R. The role of the prostaglandin system in the regulation of renal function in normal women. Am J Med. 1980 Nov;69(5):718–724. doi: 10.1016/0002-9343(80)90437-4. [DOI] [PubMed] [Google Scholar]
  11. Hall D., Zeitler H., Rudolph W. Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure. J Am Coll Cardiol. 1992 Dec;20(7):1549–1555. doi: 10.1016/0735-1097(92)90449-w. [DOI] [PubMed] [Google Scholar]
  12. Katz A. M., Messineo F. C. Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium. Circ Res. 1981 Jan;48(1):1–16. doi: 10.1161/01.res.48.1.1. [DOI] [PubMed] [Google Scholar]
  13. Kilbom A., Wennmalm A. Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia. J Physiol. 1976 May;257(1):109–121. doi: 10.1113/jphysiol.1976.sp011358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Levenson D. J., Simmons C. E., Jr, Brenner B. M. Arachidonic acid metabolism, prostaglandins and the kidney. Am J Med. 1982 Feb;72(2):354–374. doi: 10.1016/0002-9343(82)90826-9. [DOI] [PubMed] [Google Scholar]
  15. Lote C. J., Haylor J. Eicosanoids in renal function. Prostaglandins Leukot Essent Fatty Acids. 1989 Jun;36(4):203–217. doi: 10.1016/0952-3278(89)90134-8. [DOI] [PubMed] [Google Scholar]
  16. Messina E. J., Weiner R., Kaley G. Inhibition of bradykinin vasodilation and potentiation of norepinephrine and angiotensin vasoconstriction by inhibitors of prostaglandin synthesis in skeletal muscle of the rat. Circ Res. 1975 Oct;37(4):430–437. doi: 10.1161/01.res.37.4.430. [DOI] [PubMed] [Google Scholar]
  17. Moore T. J., Crantz F. R., Hollenberg N. K., Koletsky R. J., Leboff M. S., Swartz S. L., Levine L., Podolsky S., Dluhy R. G., Williams G. H. Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension. Hypertension. 1981 Mar-Apr;3(2):168–173. doi: 10.1161/01.hyp.3.2.168. [DOI] [PubMed] [Google Scholar]
  18. Nishimura H., Kubo S., Ueyama M., Kubota J., Kawamura K. Peripheral hemodynamic effects of captopril in patients with congestive heart failure. Am Heart J. 1989 Jan;117(1):100–105. doi: 10.1016/0002-8703(89)90662-5. [DOI] [PubMed] [Google Scholar]
  19. Oliver J. A., Sciacca R. R., Pinto J., Cannon P. J. Participation of the prostaglandins in the control of renal blood flow during acute reduction of cardiac output in the dog. J Clin Invest. 1981 Jan;67(1):229–237. doi: 10.1172/JCI110018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shemesh O., Golbetz H., Kriss J. P., Myers B. D. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int. 1985 Nov;28(5):830–838. doi: 10.1038/ki.1985.205. [DOI] [PubMed] [Google Scholar]
  21. Simon L. S., Mills J. A. Drug therapy: nonsteroidal antiinflammatory drugs (first of two parts). N Engl J Med. 1980 May 22;302(21):1179–1185. doi: 10.1056/NEJM198005223022105. [DOI] [PubMed] [Google Scholar]
  22. Swartz S. L., Williams G. H. Angiotensin-converting enzyme inhibition and prostaglandins. Am J Cardiol. 1982 Apr 21;49(6):1405–1409. doi: 10.1016/0002-9149(82)90351-4. [DOI] [PubMed] [Google Scholar]
  23. Walshe J. J., Venuto R. C. Acute oliguric renal failure induced by indomethacin: possible mechanism. Ann Intern Med. 1979 Jul;91(1):47–49. doi: 10.7326/0003-4819-91-1-47. [DOI] [PubMed] [Google Scholar]
  24. Wennmalm A. Influence of indomethacin on the systemic and pulmonary vascular resistance in man. Clin Sci Mol Med. 1978 Feb;54(2):141–145. doi: 10.1042/cs0540141. [DOI] [PubMed] [Google Scholar]
  25. Yang H. Y., Erdös E. G., Levin Y. A dipeptidyl carboxypeptidase that converts angiotensin I and inactivates bradykinin. Biochim Biophys Acta. 1970 Aug 21;214(2):374–376. doi: 10.1016/0005-2795(70)90017-6. [DOI] [PubMed] [Google Scholar]

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