This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Andresen, B. T. Articles by Romero, G. G. Search for Related Content PubMed PubMed Citation Articles by Andresen, B. T. Articles by Romero, G. G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Cardio-renal physiology/pathophysiology Animal models of human disease Other hypertension

(Hypertension. 2001;37:635.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Angiotensin II Signaling to Phospholipase D in Renal Microvascular Smooth Muscle Cells in SHR

Bradley T. Andresen; Edwin K. Jackson; Guillermo G. Romero

From the Department of Pharmacology (B.T.A., E.K.J., G.G.R.), University of Pittsburgh, Pittsburgh, Pa.

Correspondence to Bradley T. Andreson, W1318 Biomedical Science Tower, Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15261. E-mail btast6{at}pitt.edu

Angiotensin II (Ang II)–induced phospholipase D (PLD) activity is greater in aortic smooth muscle from spontaneously hypertensive rats (SHR) versus normotensive Wistar-Kyoto rats (WKY). Whether and how this signaling pathway is altered in preglomerular microvascular smooth muscle cells (PGSMCs), a cell type that may participate in genetic hypertension, is unknown. The goals of the present study were to determine in SHR and WKY PGSMCs the following: (1) whether Ang II induces PLD activity; (2) whether the effect of Ang II on PLD activity is greater in SHR; (3) which PLD isoform is stimulated by Ang II; (4) what signaling pathway mediates Ang II–induced PLD stimulation; and (5) whether the signaling pathways mediating Ang II–induced PLD activity are different in SHR and WKY. The EC₅₀ for Ang II–induced PLD stimulation in SHR was 10-fold lower than the EC₅₀ in WKY, and both were inhibited by L-158,805, an AT₁ antagonist. Inhibitors of phosphoinositol-3-kinase and protein kinase C did not block Ang II–induced PLD activity in SHR and WKY PGSMCs. Catalytically-inactive constructs of PLD2 and RhoA, but not PLD1, ADP ribosylation factor 1 (ARF1), ARF6, or ADP ribosylation factor nucleotide exchange factor (ARNO) blocked Ang II–induced PLD activity in SHR and WKY PGSMCs. Brefeldin A completely blocked Ang II–induced PLD activity in SHR but only slightly reduced Ang II–induced PLD activity in WKY PGSMCs. Therefore, we conclude that in PGSMCs, the effect of Ang II on PLD activity is (1) greater in SHR; (2) mediated by AT₁ receptors signaling to PLD2; (3) transduced primarily by Rho proteins; and (4) inhibited in SHR by brefeldin A.

Key Words: angiotensin II • phospholipases • hypertension, experimental • RhoA • receptors, angiotensin • rats, inbred SHR • brefeldin A

This article has been cited by other articles:

				E. K. Jackson, D. G. Gillespie, C. Zhu, J. Ren, L. C. Zacharia, and Z. Mi {alpha}2-Adrenoceptors Enhance Angiotensin II-Induced Renal Vasoconstriction: Role for NADPH Oxidase and RhoA Hypertension, March 1, 2008; 51(3): 719 - 726. [Abstract] [Full Text] [PDF]

				Y. Chen, A. Pearlman, Z. Luo, and C. S. Wilcox Hydrogen peroxide mediates a transient vasorelaxation with tempol during oxidative stress Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2085 - H2092. [Abstract] [Full Text] [PDF]

				J. A. Grodnitzky, N. Syed, M. J. Kimber, T. A. Day, J. G. Donaldson, and W. H. Hsu Somatostatin Receptors Signal through EFA6A-ARF6 to Activate Phospholipase D in Clonal beta-Cells J. Biol. Chem., May 4, 2007; 282(18): 13410 - 13418. [Abstract] [Full Text] [PDF]

				W. B. Bollag, P. Kent, S. White, M. Malinova, C. M. Isales, and R. A. Calle Characterization and Phospholipase D Mediation of the Angiotensin II Priming Response in Adrenal Glomerulosa Cells Endocrinology, February 1, 2007; 148(2): 585 - 593. [Abstract] [Full Text] [PDF]

				J.-H. Parmentier, Z. Pavicevic, and K. U. Malik ANG II stimulates phospholipase D through PKC{zeta} activation in VSMC: implications in adhesion, spreading, and hypertrophy Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H46 - H54. [Abstract] [Full Text] [PDF]

				B. T. Andresen, K. Shome, E. K. Jackson, and G. G. Romero AT2 receptors cross talk with AT1 receptors through a nitric oxide- and RhoA-dependent mechanism resulting in decreased phospholipase D activity Am J Physiol Renal Physiol, April 1, 2005; 288(4): F763 - F770. [Abstract] [Full Text] [PDF]

				F. Li and K. U. Malik Angiotensin II-Induced Akt Activation through the Epidermal Growth Factor Receptor in Vascular Smooth Muscle Cells Is Mediated by Phospholipid Metabolites Derived by Activation of Phospholipase D J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1043 - 1054. [Abstract] [Full Text] [PDF]

				Z. Yang, L. D. Asico, P. Yu, Z. Wang, J. E. Jones, R.-k. Bai, D. R. Sibley, R. A. Felder, and P. A. Jose D5 dopamine receptor regulation of phospholipase D Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H55 - H61. [Abstract] [Full Text] [PDF]

				T. C. Jackson, Z. Mi, and E. K. Jackson Modulation of Cyclic AMP Production by Signal Transduction Pathways in Preglomerular Microvessels and Microvascular Smooth Muscle Cells J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 349 - 358. [Abstract] [Full Text] [PDF]

				B. T. Andresen, G. G. Romero, and E. K. Jackson AT2 Receptors Attenuate AT1 Receptor-Induced Phospholipase D Activation in Vascular Smooth Muscle Cells J. Pharmacol. Exp. Ther., April 1, 2004; 309(1): 425 - 431. [Abstract] [Full Text]

				G. Du, P. Huang, B. T. Liang, and M. A. Frohman Phospholipase D2 Localizes to the Plasma Membrane and Regulates Angiotensin II Receptor Endocytosis Mol. Biol. Cell, March 1, 2004; 15(3): 1024 - 1030. [Abstract] [Full Text] [PDF]

				M. A Frias, F. Dubouloz, M. C Rebsamen, and U. Lang Prostacyclin production in rat aortic smooth muscle cells: role of protein kinase C, phospholipase D and cyclooxygenase-2 expression Cardiovasc Res, November 1, 2003; 60(2): 438 - 446. [Abstract] [Full Text] [PDF]

				L. Gao, C. Zhu, and E. K. Jackson alpha 2-Adrenoceptors Potentiate Angiotensin II- and Vasopressin-Induced Renal Vasoconstriction in Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., May 1, 2003; 305(2): 581 - 586. [Abstract] [Full Text] [PDF]

				D. Chen, E. V. Balyakina, M. Lawrence, B. W. Christman, and B. Meyrick Cyclooxygenase is regulated by ET-1 and MAPKs in peripheral lung microvascular smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 2003; 284(4): L614 - L621. [Abstract] [Full Text] [PDF]

				B. T. Andresen, J. J. Linnoila, E. K. Jackson, and G. G. Romero Role of EGFR Transactivation in Angiotensin II Signaling to Extracellular Regulated Kinase in Preglomerular Smooth Muscle Cells Hypertension, March 1, 2003; 41(3): 781 - 786. [Abstract] [Full Text] [PDF]

				A. Cavarape, N. Endlich, R. Assaloni, E. Bartoli, M. Steinhausen, N. Parekh, and K. Endlich Rho-Kinase Inhibition Blunts Renal Vasoconstriction Induced by Distinct Signaling Pathways In Vivo J. Am. Soc. Nephrol., January 1, 2003; 14(1): 37 - 45. [Abstract] [Full Text] [PDF]

				E. K. Jackson, W. A. Herzer, C. K. Kost Jr, and S. J. Vyas Enhanced Interaction Between Renovascular {alpha}2-Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension Hypertension, September 1, 2001; 38(3): 353 - 360. [Abstract] [Full Text] [PDF]