AJP - Heart and Circulatory Physiology, Vol 257, Issue 2 434-H443, Copyright © 1989 by American Physiological Society

ARTICLES

Selective inhibition of angiotensin II-mediated vasoconstriction by lipoxygenase blockade

N. Stern, M. Golub, K. Nozawa, M. Berger, E. Knoll, N. Yanagawa, R. Natarajan, J. L. Nadler and M. L. Tuck
Department of Medicine, University of California, Los Angeles.

We have previously demonstrated that the lipoxygenase (LO) pathway has a specific role in the effect of angiotensin II (ANG II) on aldosterone secretion. To elucidate whether the LO pathway also participates in the vascular effects of ANG II, the nonselective LO inhibitor phenidone (PHE; 30 mg/kg) was administered to rats 1 h before graded dose ANG II infusion. PHE reduced the LO product 12-hydroxyeicosatetraenoic acid (12-HETE) in deendothelialized aortas by an average of 36% as determined by radiometric detection with high-performance liquid chromatography and radioimmunoassay methods. In parallel, the peak systolic pressor response to ANG II was lowered from 36.2 +/- 3.7 to 16.8 +/- 2.0 mmHg. The peak pressor responses to ANG II were also reduced by two other LO inhibitors, baicalein (30 mg/kg) and esculetin (60 mg/kg) (13.9 +/- 2.4 and 22.1 +/- 4.7 mmHg, respectively; P less than 0.01 compared with control rats for both), but not by the cyclooxygenase inhibitor indomethacin. The LO inhibitors baicalein (7.5 X 10(-5) M) and PHE (10(-4) M) markedly attenuated the in vitro contractile response to ANG II of femoral artery rings. In contrast, neither the in vivo nor in vitro constrictor responses to norepinephrine were affected by baicalein. Thus lipoxygenase blockade induces a direct and selective inhibition of ANG II-induced vasoconstriction. The LO pathway may have an important role in mediating the pressor effect of ANG II.

This article has been cited by other articles:

				S. S. Yiu, X. Zhao, E. W. Inscho, and J. D. Imig 12-Hydroxyeicosatetraenoic acid participates in angiotensin II afferent arteriolar vasoconstriction by activating L-type calcium channels J. Lipid Res., December 1, 2003; 44(12): 2391 - 2399. [Abstract] [Full Text] [PDF]

				M. Alonso-Galicia, K. G. Maier, A. S. Greene, A. W. Cowley Jr., and R. J. Roman Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R60 - R68. [Abstract] [Full Text] [PDF]

				C. Berry, R. Touyz, A. F. Dominiczak, R. C. Webb, and D. G. Johns Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2337 - H2365. [Abstract] [Full Text] [PDF]

				R. Limor, G. Weisinger, S. Gilad, E. Knoll, O. Sharon, A. Jaffe, F. Kohen, E. Berger, B. Lifschizt-Mercer, and N. Stern A Novel Form of Platelet-Type 12-Lipoxygenase mRNA in Human Vascular Smooth Muscle Cells Hypertension, October 1, 2001; 38(4): 864 - 871. [Abstract] [Full Text] [PDF]

				S. Shastri, J. R. McNeill, T. W. Wilson, R. Poduri, C. Kaul, and V. Gopalakrishnan Cysteinyl leukotrienes mediate enhanced vasoconstriction to angiotensin II but not endothelin-1 in SHR Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H342 - H349. [Abstract] [Full Text] [PDF]

				D. Gonzalez-Nunez, J. Claria, F. Rivera, and E. Poch Increased Levels of 12(S)-HETE in Patients With Essential Hypertension Hypertension, February 1, 2001; 37(2): 334 - 338. [Abstract] [Full Text] [PDF]

				E. Middleton Jr., C. Kandaswami, and T. C. Theoharides The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer Pharmacol. Rev., December 1, 2000; 52(4): 673 - 751. [Abstract] [Full Text] [PDF]

				K. D. Croft, J. C. McGiff, A. Sanchez-Mendoza, and M. A. Carroll Angiotensin II releases 20-HETE from rat renal microvessels Am J Physiol Renal Physiol, September 1, 2000; 279(3): F544 - F551. [Abstract] [Full Text] [PDF]

				H. Takizawa, A. DelliPizzi, and A. Nasjletti Prostaglandin I2 Contributes to the Vasodepressor Effect of Baicalein in Hypertensive Rats Hypertension, March 1, 1998; 31(3): 866 - 871. [Abstract] [Full Text] [PDF]

				M. N. Graber, A. Alfonso, and D. L. Gill Recovery of Ca2+ Pools and Growth in Ca2+ Pool-depleted Cells Is Mediated by Specific Epoxyeicosatrienoic Acids Derived from Arachidonic Acid J. Biol. Chem., November 21, 1997; 272(47): 29546 - 29553. [Abstract] [Full Text] [PDF]

				R. Natarajan, W. Bai, L. Lanting, N. Gonzales, and J. Nadler Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2224 - H2231. [Abstract] [Full Text] [PDF]

				R. Natarajan, J. Rosdahl, N. Gonzales, and W. Bai Regulation of 12-Lipoxygenase by Cytokines in Vascular Smooth Muscle Cells Hypertension, October 1, 1997; 30(4): 873 - 879. [Abstract] [Full Text]

				E. S. Kisch, A. Jaffe, E. Knoll, and N. Stern Role of the Lipoxygenase Pathway in Angiotensin II–Induced Vasoconstriction in the Human Placenta Hypertension, March 1, 1997; 29(3): 796 - 801. [Abstract] [Full Text]

				H. J. Oskarsson and D. D. Heistad Oxidative Stress Produced by Angiotensin Too: Implications for Hypertension and Vascular Injury Circulation, February 4, 1997; 95(3): 557 - 559. [Full Text]

				J. A. Kim, J.-L. Gu, R. Natarajan, J. A. Berliner, and J. L. Nadler A Leukocyte Type of 12-Lipoxygenase Is Expressed in Human Vascular and Mononuclear Cells : Evidence for Upregulation by Angiotensin II Arterioscler. Thromb. Vasc. Biol., July 1, 1995; 15(7): 942 - 948. [Abstract] [Full Text]

				J.-L. Gu, D. Veerapanane, J. Rossi, R. Natarajan, L. Thomas, and J. Nadler Ribozyme-Mediated Inhibition of Expression of Leukocyte-type 12-Lipoxygenase in Porcine Aortic Vascular Smooth Muscle Cells Circ. Res., July 1, 1995; 77(1): 14 - 20. [Abstract] [Full Text]