Abstract
The objective of this study was to determine whether arachidonate metabolites are involved in the vasoconstrictive effects of angiotensin II in rats. In the isolated perfused heart, dexamethasone (4 mg/kg) significantly suppressed the maximal decreases in coronary flow induced by angiotensin II and vasopressin (reference drug). In the heart, the nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1 μM) markedly suppressed the angiotensin II-induced decreases in coronary flow. NDGA (10 μM) inhibited both angiotensin II- and methoxamine- (reference drug) induced contractions in aortic rings with (in the presence of L-NAME) and without endothelium. In the heart, the leukotriene synthesis inhibitor MK-886 (0.3 μM) significantly reduced the maximal effects to angiotensin II, but the leukotriene antagonist FPL 55712 (0.1 and 0.3 μM) had no effect. We conclude that in the isolated perfused rat heart angiotensin II-induced decreases in coronary flow are in part mediated by Hpoxygenase products, which might be derived from the 5-Hpoxygenase pathway, but are probably not leukotrienes. Furthermore, endothelium independent Hpoxygenase products mediate part of the contractile responses to angiotensin II in the isolated rat aorta.
Full Text
The Full Text of this article is available as a PDF (970.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Antonipillai I., Nadler J., Horton R. Angiotensin feedback inhibition on renin is expressed via the lipoxygenase pathway. Endocrinology. 1988 Apr;122(4):1277–1281. doi: 10.1210/endo-122-4-1277. [DOI] [PubMed] [Google Scholar]
- Ashida Y., Saijo T., Kuriki H., Makino H., Terao S., Maki Y. Pharmacological profile of AA-861, a 5-lipoxygenase inhibitor. Prostaglandins. 1983 Dec;26(6):955–972. doi: 10.1016/0090-6980(83)90157-0. [DOI] [PubMed] [Google Scholar]
- Baker K. M., Aceto J. F. Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells. Am J Physiol. 1990 Aug;259(2 Pt 2):H610–H618. doi: 10.1152/ajpheart.1990.259.2.H610. [DOI] [PubMed] [Google Scholar]
- Bell-Quilley C. P., Lin Y. S., Hilchey S. D., Drugge E. D., McGiff J. C. Renovascular actions of angiotensin II in the isolated kidney of the rat: relationship to lipoxygenases. J Pharmacol Exp Ther. 1993 Nov;267(2):676–682. [PubMed] [Google Scholar]
- Blackwell G. J., Carnuccio R., Di Rosa M., Flower R. J., Parente L., Persico P. Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids. Nature. 1980 Sep 11;287(5778):147–149. doi: 10.1038/287147a0. [DOI] [PubMed] [Google Scholar]
- Deblois D., Bouthillier J., Marceau F. Effect of glucocorticoids, monokines and growth factors on the spontaneously developing responses of the rabbit isolated aorta to des-Arg9-bradykinin. Br J Pharmacol. 1988 Apr;93(4):969–977. doi: 10.1111/j.1476-5381.1988.tb11487.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farber H. W., Center D. M., Rounds S. Bovine and human endothelial cell production of neutrophil chemoattractant activity in response to components of the angiotensin system. Circ Res. 1985 Dec;57(6):898–902. doi: 10.1161/01.res.57.6.898. [DOI] [PubMed] [Google Scholar]
- Kaski J. C., Rosano G., Gavrielides S., Chen L. Effects of angiotensin-converting enzyme inhibition on exercise-induced angina and ST segment depression in patients with microvascular angina. J Am Coll Cardiol. 1994 Mar 1;23(3):652–657. doi: 10.1016/0735-1097(94)90750-1. [DOI] [PubMed] [Google Scholar]
- Lindpaintner K., Jin M., Wilhelm M. J., Suzuki F., Linz W., Schoelkens B. A., Ganten D. Intracardiac generation of angiotensin and its physiologic role. Circulation. 1988 Jun;77(6 Pt 2):I18–I23. [PubMed] [Google Scholar]
- Miller D. K., Gillard J. W., Vickers P. J., Sadowski S., Léveillé C., Mancini J. A., Charleson P., Dixon R. A., Ford-Hutchinson A. W., Fortin R. Identification and isolation of a membrane protein necessary for leukotriene production. Nature. 1990 Jan 18;343(6255):278–281. doi: 10.1038/343278a0. [DOI] [PubMed] [Google Scholar]
- Naccache P. H., Showell H. J., Becker E. L., Sha'afi R. I. Pharmacological differentiation between the chemotactic factor induced intracellular calcium redistribution and transmembrane calcium influx in rabbit neutrophils. Biochem Biophys Res Commun. 1979 Aug 28;89(4):1224–1230. doi: 10.1016/0006-291x(79)92139-9. [DOI] [PubMed] [Google Scholar]
- Nadler J. L., Natarajan R., Stern N. Specific action of the lipoxygenase pathway in mediating angiotensin II-induced aldosterone synthesis in isolated adrenal glomerulosa cells. J Clin Invest. 1987 Dec;80(6):1763–1769. doi: 10.1172/JCI113269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Natarajan R., Gonzales N., Hornsby P. J., Nadler J. Mechanism of angiotensin II-induced proliferation in bovine adrenocortical cells. Endocrinology. 1992 Sep;131(3):1174–1180. doi: 10.1210/endo.131.3.1505459. [DOI] [PubMed] [Google Scholar]
- Natarajan R., Gonzales N., Lanting L., Nadler J. Role of the lipoxygenase pathway in angiotensin II-induced vascular smooth muscle cell hypertrophy. Hypertension. 1994 Jan;23(1 Suppl):I142–I147. doi: 10.1161/01.hyp.23.1_suppl.i142. [DOI] [PubMed] [Google Scholar]
- Natarajan R., Gu J. L., Rossi J., Gonzales N., Lanting L., Xu L., Nadler J. Elevated glucose and angiotensin II increase 12-lipoxygenase activity and expression in porcine aortic smooth muscle cells. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4947–4951. doi: 10.1073/pnas.90.11.4947. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Natarajan R., Stern N., Hsueh W., Do Y., Nadler J. Role of the lipoxygenase pathway in angiotensin II-mediated aldosterone biosynthesis in human adrenal glomerulosa cells. J Clin Endocrinol Metab. 1988 Sep;67(3):584–591. doi: 10.1210/jcem-67-3-584. [DOI] [PubMed] [Google Scholar]
- Piomelli D., Greengard P. Lipoxygenase metabolites of arachidonic acid in neuronal transmembrane signalling. Trends Pharmacol Sci. 1990 Sep;11(9):367–373. doi: 10.1016/0165-6147(90)90182-8. [DOI] [PubMed] [Google Scholar]
- Rhaleb N. E., Rouissi N., Nantel F., D'Orléans-Juste P., Regoli D. DuP 753 is a specific antagonist for the angiotensin receptor. Hypertension. 1991 Apr;17(4):480–484. doi: 10.1161/01.hyp.17.4.480. [DOI] [PubMed] [Google Scholar]
- Rouzer C. A., Ford-Hutchinson A. W., Morton H. E., Gillard J. W. MK886, a potent and specific leukotriene biosynthesis inhibitor blocks and reverses the membrane association of 5-lipoxygenase in ionophore-challenged leukocytes. J Biol Chem. 1990 Jan 25;265(3):1436–1442. [PubMed] [Google Scholar]
- Saito F., Hori M. T., Ideguchi Y., Berger M., Golub M., Stern N., Tuck M. L. 12-Lipoxygenase products modulate calcium signals in vascular smooth muscle cells. Hypertension. 1992 Aug;20(2):138–143. doi: 10.1161/01.hyp.20.2.138. [DOI] [PubMed] [Google Scholar]
- Stern N., Golub M., Nozawa K., Berger M., Knoll E., Yanagawa N., Natarajan R., Nadler J. L., Tuck M. L. Selective inhibition of angiotensin II-mediated vasoconstriction by lipoxygenase blockade. Am J Physiol. 1989 Aug;257(2 Pt 2):H434–H443. doi: 10.1152/ajpheart.1989.257.2.H434. [DOI] [PubMed] [Google Scholar]
- Vleeming W., van der Wouw P. A., van Rooij H. H., Wemer J., Porsius A. J. In vitro method for measurement of cardiac performance and responses to inotropic drugs after experimentally induced myocardial infarction in the rat. J Pharmacol Methods. 1989 Apr;21(2):95–102. doi: 10.1016/0160-5402(89)90027-2. [DOI] [PubMed] [Google Scholar]
