Abstract
1. The haemodynamic effects of calcium antagonists could depend at least in part on the activity of vasoactive prostanoids. 2. We set out to study the effect of the cyclo-oxygenase inhibitor ibuprofen, 400 mg three times daily for 3 days, by a randomised cross-over study vs placebo in 12 mild to moderate essential hypertensive patients who had been treated for 1 month with amlodipine. 3. Blood pressure, heart rate and vascular resistances in the upper limb (Doppler ultrasound) were measured. Plasma renin activity and urinary aldosterone, as well as indices of renal function, were evaluated. Urinary 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TXB2, as well as 6-keto-PGF1 alpha and TXB2, were measured as indices of systemic and renal PGI2 and TXA2 synthesis. 4. Amlodipine normalised blood pressure and reduced upper limb vascular resistances; it did not affect urinary prostanoid excretion. Short-term combined administration of ibuprofen resulted in, by comparison with placebo, inhibition of systemic PGI2 (-80.5 ng 24 h-1, 95% CI -99.2, -61.4; P < 0.001) and TXA2 (-216.1 ng 24 h-1, 95% CI -276.5, -155.8; P < 0.001), together with an increase in systolic (+7.8 mm Hg, 95% CI +3.1, +12.3; P < 0.01) and diastolic (+3.9 mm Hg, 95% CI +1.2, +6.6; P < 0.01) blood pressure; it had no significant effect on regional vascular resistances (+4.7 mm Hg ml-1 s, 95% CI -5.6, +15.0). Effects of ibuprofen on renal prostanoid synthesis were less marked, and there was no change in indices of renal function or hydro-electrolytic balance.(ABSTRACT TRUNCATED AT 250 WORDS)
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arosio E., Pancera P., Arcaro G., Priante F., Montesi G., Zannoni M., Lechi A. Effects of long-term nicardipine treatment on hemodynamics of large arteries in essential hypertension. Cardiovasc Drugs Ther. 1989 Dec;3(6):835–839. doi: 10.1007/BF01869568. [DOI] [PubMed] [Google Scholar]
- Brown J., Dollery C., Valdes G. Interaction of nonsteroidal anti-inflammatory drugs with antihypertensive and diuretic agents. Control of vascular reactivity by endogenous prostanoids. Am J Med. 1986 Aug 25;81(2B):43–57. doi: 10.1016/0002-9343(86)90907-1. [DOI] [PubMed] [Google Scholar]
- Carmines P. K., Mitchell K. D., Navar L. G. Effects of calcium antagonists on renal hemodynamics and glomerular function. Kidney Int Suppl. 1992 May;36:S43–S48. [PubMed] [Google Scholar]
- Catella F., Nowak J., Fitzgerald G. A. Measurement of renal and non-renal eicosanoid synthesis. Am J Med. 1986 Aug 25;81(2B):23–29. doi: 10.1016/0002-9343(86)90905-8. [DOI] [PubMed] [Google Scholar]
- Faulkner J. K., McGibney D., Chasseaud L. F., Perry J. L., Taylor I. W. The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. Br J Clin Pharmacol. 1986 Jul;22(1):21–25. doi: 10.1111/j.1365-2125.1986.tb02874.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frölich J. C., Förstermann U. Role of eicosanoids in regulation of vascular resistance. Adv Prostaglandin Thromboxane Leukot Res. 1989;19:211–215. [PubMed] [Google Scholar]
- Furst D. E. Use of ibuprofen in unusual circumstances. Am J Med. 1984 Jul 13;77(1A):51–56. doi: 10.1016/s0002-9343(84)80019-4. [DOI] [PubMed] [Google Scholar]
- Hills M., Armitage P. The two-period cross-over clinical trial. Br J Clin Pharmacol. 1979 Jul;8(1):7–20. doi: 10.1111/j.1365-2125.1979.tb05903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Houston M. C. Nonsteroidal anti-inflammatory drugs and antihypertensives. Am J Med. 1991 May 17;90(5A):42S–47S. doi: 10.1016/0002-9343(91)90485-g. [DOI] [PubMed] [Google Scholar]
- Larochelle P. Renal tubular effects of calcium antagonists. Kidney Int Suppl. 1992 May;36:S49–S53. [PubMed] [Google Scholar]
- Malik K. U. Interaction of arachidonic acid metabolites and adrenergic nervous system. Am J Med Sci. 1988 Apr;295(4):280–286. doi: 10.1097/00000441-198804000-00011. [DOI] [PubMed] [Google Scholar]
- Minuz P., Barrow S. E., Cockcroft J. R., Ritter J. M. Effects of non-steroidal anti-inflammatory drugs on prostacyclin and thromboxane biosynthesis in patients with mild essential hypertension. Br J Clin Pharmacol. 1990 Oct;30(4):519–526. doi: 10.1111/j.1365-2125.1990.tb03809.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Mulvany M. J. The development and regression of vascular hypertrophy. J Cardiovasc Pharmacol. 1992;19 (Suppl 2):S22–S27. doi: 10.1097/00005344-199219002-00006. [DOI] [PubMed] [Google Scholar]
- Murphy M. B., Orchard M. A., Conway E. L., Barrow S. E. The effects of nifedipine on platelet aggregation and plasma 6-keto-PGF1 alpha, and its interaction with indomethacin. Eur J Clin Pharmacol. 1985;29(4):413–416. doi: 10.1007/BF00613454. [DOI] [PubMed] [Google Scholar]
- Negus P., Tannen R. L., Dunn M. J. Indomethacin potentiates the vasoconstrictor actions of angiotensin II in normal man. Prostaglandins. 1976 Aug;12(2):175–180. doi: 10.1016/0090-6980(76)90111-8. [DOI] [PubMed] [Google Scholar]
- Oates J. A., Whorton A. R., Gerkens J. F., Branch R. A., Hollifield J. W., Frölich J. C. The participation of prostaglandins in the control of renin release. Fed Proc. 1979 Jan;38(1):72–74. [PubMed] [Google Scholar]
- Passmore A. P., Copeland S., Johnston G. D. The effects of ibuprofen and indomethacin on renal function in the presence and absence of frusemide in healthy volunteers on a restricted sodium diet. Br J Clin Pharmacol. 1990 Mar;29(3):311–319. doi: 10.1111/j.1365-2125.1990.tb03641.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patak R. V., Mookerjee B. K., Bentzel C. J., Hysert P. E., Babej M., Lee J. B. Antagonism of the effects of furosemide by indomethacin in normal and hypertensive man. Prostaglandins. 1975 Oct;10(4):649–659. doi: 10.1016/s0090-6980(75)80012-8. [DOI] [PubMed] [Google Scholar]
- Radack K. L., Deck C. C., Bloomfield S. S. Ibuprofen interferes with the efficacy of antihypertensive drugs. A randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen. Ann Intern Med. 1987 Nov;107(5):628–635. doi: 10.7326/0003-4819-107-5-628. [DOI] [PubMed] [Google Scholar]
- Salvetti A., Arzilli F., Pedrinelli R., Beggi P., Motolese M. Interaction between oxprenolol and indomethacin on blood pressure in essential hypertensive patients. Eur J Clin Pharmacol. 1982;22(3):197–201. doi: 10.1007/BF00545214. [DOI] [PubMed] [Google Scholar]
- Salvetti A., Magagna A., Abdel-Haq B., Lenzi M., Giovannetti R. Nifedipine interactions in hypertensive patients. Cardiovasc Drugs Ther. 1990 Aug;4 (Suppl 5):963–968. doi: 10.1007/BF02018301. [DOI] [PubMed] [Google Scholar]
- Salvetti A., Pedrinelli R., Magagna A., Stornello M., Scapellato L. Calcium antagonists: interactions in hypertension. Am J Nephrol. 1986;6 (Suppl 1):95–99. doi: 10.1159/000167228. [DOI] [PubMed] [Google Scholar]
- Wong D. G., Spence J. D., Lamki L., Freeman D., McDonald J. W. Effect of non-steroidal anti-inflammatory drugs on control of hypertension by beta-blockers and diuretics. Lancet. 1986 May 3;1(8488):997–1001. doi: 10.1016/s0140-6736(86)91271-7. [DOI] [PubMed] [Google Scholar]
- de Nucci G., Thomas R., D'Orleans-Juste P., Antunes E., Walder C., Warner T. D., Vane J. R. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9797–9800. doi: 10.1073/pnas.85.24.9797. [DOI] [PMC free article] [PubMed] [Google Scholar]