Abstract
Gq-protein is located at the convergent point in signal transduction pathways leading to vascular remodeling. The carboxyl terminus of Gα-subunit plays a vital role in G-protein-receptor interaction. The present study was designed to explore the effects of a synthetic Gαq carboxyl terminus imitation peptide, namely GCIP-27, on vascular smooth muscle cells (VSMC) in vitro and vascular remodeling in spontaneous hypertensive rats (SHR). Hyperplasia and hypertrophy of VSMC wre determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, [(3)H]-thymidine and [(3)H]-leucine incorporation, and [Ca(2+)](i) was measured with Fluo-3/AM staining. Systolic blood pressure (SBP), the ratio of media thickness to lumen diameter (MT/LD) of aorta, collagen content, and phospholipase C activity in aorta were measured in SHR. GCIP-27 (3-100 µg/l) significantly decreased proliferation activity, protein content, incorporation of [(3)H]-thymidine and [(3)H]-leucine, and [Ca(2+)](i) level in VSMC. SBP, MT/LD, collagen content, and phospholipase C activity in aorta of SHR were decreased significantly in GCIP-27 (7, 20, 60 µg/kg)-treated groups and losartan (6 mg/kg) group compared with vehicle group. In conclusion, GCIP-27 could inhibit vascular remodeling effectively in vitro and in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Angiotensin II / pharmacology
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Angiotensin II Type 1 Receptor Blockers / pharmacology
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Animals
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Aorta / cytology
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Aorta / metabolism
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Aorta / pathology*
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Aorta / physiopathology
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Blood Pressure / drug effects
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Blood Pressure / physiology
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Blood Pressure Determination
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Calcium / analysis
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Cardiotonic Agents / pharmacology*
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Cardiotonic Agents / therapeutic use
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Cell Culture Techniques
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Cell Proliferation / drug effects*
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Collagen / metabolism
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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GTP-Binding Protein alpha Subunits, Gq-G11 / physiology
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GTP-Binding Protein alpha Subunits, Gq-G11 / therapeutic use*
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Hypertension / drug therapy
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Hypertension / metabolism
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Hypertension / pathology*
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Hypertension / physiopathology
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Hypertrophy / pathology*
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Hypertrophy / physiopathology
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Losartan / pharmacology
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Male
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Mice
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Molecular Targeted Therapy
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism
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Muscle, Smooth, Vascular / pathology*
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Myocytes, Smooth Muscle / cytology
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Myocytes, Smooth Muscle / metabolism
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Myocytes, Smooth Muscle / pathology*
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Peptides / pharmacology*
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Random Allocation
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Rats
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Rats, Inbred SHR
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Rats, Inbred WKY
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Rats, Wistar
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Tetrazolium Salts
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Thiazoles
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Type C Phospholipases / metabolism
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Vasoconstrictor Agents / pharmacology
Substances
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Angiotensin II Type 1 Receptor Blockers
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Cardiotonic Agents
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GCIP-27 peptide
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Peptides
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Tetrazolium Salts
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Thiazoles
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Vasoconstrictor Agents
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Angiotensin II
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Collagen
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Type C Phospholipases
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GTP-Binding Protein alpha Subunits, Gq-G11
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thiazolyl blue
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Losartan
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Calcium