Inhibition of left ventricular remodelling in spontaneously hypertensive rats by G alpha q-protein carboxyl terminus imitation polypeptide GCIP-27 is not entirely dependent on blood pressure.
The G(q)-protein is located at the convergent point in the signal transduction pathway that leads to ventricular remodelling. In G-protein signalling pathways, the carboxyl terminus of the G(alpha)-subunit plays a vital role in G-protein-receptor interaction. The aim of the present study was to explore the effects of a synthetic G(alphaq) carboxyl terminus imitation peptide, namely GCIP-27, on left ventricular (LV) remodelling and blood pressure in spontaneous hypertensive rats (SHR). In the present study, 10, 30 or 90 microg/kg, i.p., GCIP-27 was administered for 8 weeks to SHR. In addition, another two groups of SHR were treated with either 6 mg/kg losartan or vehicle (saline). Wistar-Kyoto rats were used as controls. Systolic blood pressure (SBP) was measured using the standard tail-cuff method once every 2 weeks. At the end of the experiment, the LV mass index (LVMI) was evaluated. In addition, LV structure and function, collagen content, microstructure and ultrastructure were examined using echocardiography, the hydroxyproline assay, routine light microscopy and transmission electron microscopy, respectively. In the losartan- and GCIP-27 (10, 30 and 90 microg/kg)-treated groups, SBP was decreased significantly compared with that of the vehicle (saline) group. However, even at the highest concentration used, the hypotensive effect of GCIP-27 was weaker than that of losartan. For example, after 8 weeks treatment, SBP had decreased by 30.4% in the losartan-treated group compared with decreases of 10.5, 13.1 and 18.5% in the 10, 30 and 90 microg/kg GCIP-27-treated groups, respectively. Both GCIP-27 (10, 30 and 90 microg/kg) and losartan (6 mg/kg) significantly reduced LV posterior wall thickness, the thickness of the interventricular septum, collagen content and LVMI, with the effects of GCIP-27 at all three concentrations tested being greater than those of losartan. In conclusion, GCIP-27 effectively attenuates LV remodelling in SHR and the antiremodelling effect may not be dependent entirely on decreases in blood pressure.
Wang
Xiu-Qin
XQ
Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, China.
Zhang
Hai-Gang
HG
Cheng
Yi-Qun
YQ
Li
Xiao-Hui
XH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000138:chemical synthesis* / Q000627:therapeutic use*; D019204:GTP-Binding Proteins / Q000138:chemical synthesis* / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018716:Molecular Mimicry / Q000502:physiology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
C488275:G protein competitive inhibitory polypeptide, rat; D010446:Peptide Fragments; D019204:GTP-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11