Galphaq-protein carboxyl terminus imitation polypeptide (GCIP)-27 inhibits right ventricular hypertrophy induced by monocrotaline in rats.
This study was to investigate the probable inhibitory effect of Galphaq-protein carboxyl terminus imitation polypeptide-27 (GCIP-27), the optimized form of GCIP, which is a competition candidate of the activated binding sites on Galphaq, on the right ventricular (RV) hypertrophy induced by monocrotaline (MCT) in rats. We have previously shown that GCIP-27, can prevent the hypertrophyc responses in cultured rat cardiomyocytes induced by noradrenaline and angiotensin II. Male Sprague-Dawley rats were given a single dose (50 mg/kg) of MCT subcutaneouly to induce pulmonary hypertension (PH) and RV hypertrophy. GCIP-27 (30, 90 microg/kg) or vehicle was administered (twice daily, intraperitoneally) from day 1 to day 21. GCIP-27 (90 microg/kg) inhibited the elevated pulmonary arteria systolic pressure (PASP) and mean pulmonary arteria pressure induced by MCT, but its dose at 30 microg/kg only reduced the elevated PASP. And no effect could be seen on the pulmonary arteria diastolic pressure at both two doses. On the other hand, the two doses of GCIP-27 improved significantly the weight ratio of RV to left ventricle plus septum, the RV free wall thickness and pulmonary arteria acceleration time (PAAT). In morphometric observation, GCIP-27 (30, 90g/kg) could attenuate cardiomyocytes hypertrophy, interstitium fibrosis, mitochondria swelling and malformation markedly in RVs of MCT-treated rats. Furthermore, GCIP-27 (30, 90 mug/kg) significantly reduced the overexpression of the proliferating cell nuclear antigen (PCNA) induced by MCT in RV cardiocytes. The results suggest that GCIP-27 can effectively attenuate the RV hypertrophy induced by MCT in rats, which may be mediated by both the direct effect on cardiomyocyte and the secondary effect by reducing PH, and may be involved in its influence on the Gq signal pathway.
Yang
Dan-Li
DL
Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, China.
Zhang
Hai-Gang
HG
Xu
Ya-Li
YL
Gao
Yun-Hua
YH
Yang
Xiao-Jiao
XJ
Hao
Xue-Qin
XQ
Su
Min
M
Wang
Xiu-Qin
XQ
Li
Xiao-Hui
XH
D000818:Animals; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000737:chemistry*; D006439:Hemodynamics; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D016686:Monocrotaline; D032342:Muscle Cells / Q000648:ultrastructure; D009206:Myocardium / Q000648:ultrastructure; D010446:Peptide Fragments / Q000737:chemistry / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D010446:Peptide Fragments; D018809:Proliferating Cell Nuclear Antigen; D016686:Monocrotaline; D043802:GTP-Binding Protein alpha Subunits, Gq-G11