Published Online
on May 3, 2004

A more recent version of this article appeared on June 1, 2004

This Article Full Text (PDF) All Versions of this Article: 43/6/1258    most recent 01.HYP.0000128022.24598.4fv1 Alert me when this article is cited Alert me if a correction is posted 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 Hiyoshi, H. Articles by Okamoto, H. Search for Related Content PubMed PubMed Citation Articles by Hiyoshi, H. Articles by Okamoto, H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB LOSARTAN POTASSIUM NITRIC OXIDE Related Collections ACE/Angiotension receptors Gene expression Receptor pharmacology Endothelium/vascular type/nitric oxide

Submitted on February 26, 2004
Revised on March 15, 2004

Stimulation of Cyclic GMP Production via AT₂ and B₂ Receptors in the Pressure-Overloaded Aorta After Banding

Hiromi Hiyoshi; Katsutoshi Yayama; Masaoki Takano; and Hiroshi Okamoto^*

From the Department of Pharmacology, Faculty of Pharmaceutical Sciences and High Technology, Research Center, Kobe Gakuin University, Japan.

^* To whom correspondence should be addressed. E-mail: p-okamoto{at}kobegakuin.ac.jp.

Abstract--Abdominal aortic banding induces upregulation of the angiotensin II (Ang II) type-2 (AT₂) receptor, thereby decreasing the contractile response to Ang II in the thoracic aorta of the rat. The aim of this study was to use a mouse model to clarify the mechanisms by which the banding elicits upregulation of the aortic AT₂ receptor and the subsequent attenuation of Ang II responsiveness. Concomitantly with the elevation in blood pressure and plasma renin concentration after banding, AT₂-receptor mRNA levels in the thoracic aorta rapidly increased in mice within 4 days. Upregulation of the AT₂ receptor, as well as blood pressure elevation after banding, was abolished by losartan administration. The contractile response to Ang II was depressed in aortic rings of banding mice but not of sham mice, and was restored by either the AT₂-receptor antagonist PD123319 or the bradykinin B₂-receptor antagonist icatibant. cGMP content in the thoracic aorta of banding mice was 9-fold greater than that of sham mice, and the elevation was reduced to sham levels 1 hour after intravenous injection of PD123319 or icatibant. When aortic rings were incubated with Ang II, cGMP content increased in banding rings but not in sham rings; the pretreatment with PD123319 or icatibant inhibited Ang II-induced cGMP production. These results suggest that aortic banding induces upregulation of the AT₂ receptor through increased circulating Ang II via the AT₁ receptor, thereby activating a vasodilatory pathway in vessels through the AT₂ receptor via the kinin/cGMP system.

Key words: receptors, angiotensin II • bradykinin • nitric oxide • cyclic GMP • vasodilation

This article has been cited by other articles:

				N. Toda, K. Ayajiki, and T. Okamura Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation Pharmacol. Rev., March 1, 2007; 59(1): 54 - 87. [Abstract] [Full Text] [PDF]

				K. Yayama, H. Hiyoshi, D. Imazu, and H. Okamoto Angiotensin II Stimulates Endothelial NO Synthase Phosphorylation in Thoracic Aorta of Mice With Abdominal Aortic Banding Via Type 2 Receptor Hypertension, November 1, 2006; 48(5): 958 - 964. [Abstract] [Full Text] [PDF]

				R. M. Carey and J. Park Role of Angiotensin Type 2 Receptors in Vasodilation of Resistance and Capacitance Vessels Hypertension, November 1, 2006; 48(5): 824 - 825. [Full Text] [PDF]

				R. M. Carey Cardiovascular and Renal Regulation by the Angiotensin Type 2 Receptor: The AT2 Receptor Comes of Age Hypertension, May 1, 2005; 45(5): 840 - 844. [Full Text] [PDF]

				H. Hiyoshi, K. Yayama, M. Takano, and H. Okamoto Angiotensin Type 2 Receptor-Mediated Phosphorylation of eNOS in the Aortas of Mice With 2-Kidney, 1-Clip Hypertension Hypertension, May 1, 2005; 45(5): 967 - 973. [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]