title: Angiotensin-(1-7) inhibits angiotensin II-induced signal transduction.
abstract: The inhibitory effects of angiotensin-(1-7) on angiotensin II-induced vasoconstriction, growth of vascular smooth muscle cells, stimulation of protein kinase C, extracellular signal-regulated kinases (ERK), and angiotensin subtype 1 receptor (AT1) and subtype 2 receptor (AT2) mRNA expression were investigated. The hemodynamic effects of angiotensin-(1-7) were measured in Wistar rats. Vasoconstriction was measured using aortic rings. DNA synthesis or protein synthesis was measured in cultured vascular smooth muscle cells using [3H] thymidine or [3H] leucine incorporation, respectively. Angiotensin II stimulated protein kinase C and ERK1/2 were measured by Western blot analysis using phosphospecific protein kinase C and ERK1/2 antibodies. AT1 and AT2 receptor mRNA expression was measured using reverse-transcription polymerase chain reaction. Infusion of angiotensin II significantly increased whereas infusion of angiotensin-(1-7) had no effects on mean arterial blood pressure in Wistar rats. Angiotensin-(1-7) dose-dependently showed partial antagonism on angiotensin II-induced contraction of aortic rings. Angiotensin-(1-7) showed partial antagonism on angiotensin II-induced DNA synthesis and protein synthesis. Angiotensin-(1-7) showed partial antagonism on angiotensin II-induced activation of protein kinase C and ERK1/2. The administration of angiotensin-(1-7) showed partial antagonism on angiotensin II-induced downregulation of AT1 receptor mRNA expression, whereas AT2 receptor mRNA expression was unchanged. Angiotensin-(1-7) showed partial antagonism on angiotensin II-induced intracellular signal transduction and may play a crucial role in the adaptation process of AT1 receptors to sustained stimulation of angiotensin II.
authors.affiliation: Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing, Peoples Republic of China. zhuzm@cta.cq.cn
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.forename: Shanjun
authors.initials: S
authors.lastname: Zhu
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.forename: Markus
authors.initials: M
authors.lastname: Van Der Giet
authors.forename: Martin
authors.initials: M
authors.lastname: Tepel
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000803:Angiotensin I; D020928:Mitogen-Activated Protein Kinases; C118790:angiotensin I (1-7)