Mesenteric artery remodeling and effects of imidapril and irbesartan on it in spontaneously hypertensive rats.
OBJECTIVE
To investigate the remodeling of mesenteric artery and the expression of TGF-beta1, c-Jun in mesenteric artery and effects of imidapril and irbesartan on the remodeling in spontaneously hypertensive rats (SHR).


METHODS
Thirty SHR (male/female, 21/9), aged 13 wk, were randomly divided into 3 groups (7 male rats and 3 female rats each group): SHR group, imidapril group (imidapril 3 mg/kg.d was given in drinking water for 14 wk), and irbesartan group (irbesartan 50 mg/kg.d was given in drinking water foe 14 wk). Ten homogeneous Wistar Kyoto rats, 5 males and 5 females, weighing 206+/-49 g, were selected as normal control group (WKY group). Systolic pressure was measured on d 1, 2, 4, 6, 8, 10, 12 and 14 during the experiment and the rats were killed at the end of the experiment. Angiotensin II (Ang II) level in plasma and mesenteric arteries was measured by radioimmunoassay. The morphology of the secondary branches of mesenteric artery were examined by light microscopy and electron microscopy. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of transforming growth factor TGF-beta1 and c-Jun mRNA.


RESULTS
Compared with imidapril group and irbesartan group, the blood pressure was remarkably increased in SHR group. Ang II level in plasma and mesenteric arteries in SHR group was the same or lower than that in WKY group, and was higher in irbesartan group and lower in imidapril group. The remodeling of mesenteric arteries in SHR group was mostly obvious among the 4 groups. The ratio of TGF-beta1 absorbed light value to GAPDH absorbed light value in the SHR group was 0.887+/-0.019, which was significantly higher than that in WKY group, imidapril group, and irbesartan group with the ratios of 0.780+/-0.018, 0.803+/-0.005, and 0.847+/-0.017, respectively (P<0.01). Ang II level in plasma and mesenteric arteries in imidapril group was significantly lower than that in irbesartan group (P<0.05). The c-Jun absorbed light value/GAPDH absorbed light value of mesenteric arteries in the SHR group was 0.850+/-0.015, which was significantly higher than that in the WKY, imidapril, and irbesartan groups (0.582+/-0.013, 0.743+/-0.012, and 0.789+/-0.013, respectively, P<0.01), and was significantly lower in imidapril group than in irbesartan group (P<0.05).


CONCLUSIONS
Imidapril and irbesartan can not only control blood pressure but also inhibit mesenteric arteries remodeling and mRNA expression of TGF-beta1, c-Jun in SHR. Imidapril is more effective than irbesartan.
Zhu
Zhong-Sheng
ZS
Department of Cardiovascular Medicine, Third Affiliated Hospital of Nanjing Medical University, Nanjing 210006, Jiangsu Province, China. zhuzhongsheng6966@hotmail.com
Wang
Jin-Ming
JM
Chen
Shao-Liang
SL
D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D048289:Imidazolidines / Q000494:pharmacology*; D000077405:Irbesartan; D008297:Male; D008638:Mesenteric Arteries / Q000033:anatomy & histology* / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D048289:Imidazolidines; D016755:Proto-Oncogene Proteins c-jun; C508960:TGFB1 protein, human; D013777:Tetrazoles; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; C065166:imidapril; D000077405:Irbesartan