کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2574785 | 1561276 | 2009 | 6 صفحه PDF | دانلود رایگان |

We found previously that selective blockade of endothelin ETA receptors is superior to nonselective ETA/ETB in attenuating hypertension and survival rate in Ren-2 transgenic rats (TGR). In the present pilot study, we were interested in whether similar effects will be found in TGR with inducible malignant hypertension (iTGR; official strain name Cyp1A1-Ren-2rats), which were derived from the original Ren-2 transgenic rat strain. Studies were performed in three-month old male iTGR. Treatment with either bosentan, a non-selective ETA/ETB, or with atrasentan, a selective ETA receptor blocker, was started on day 2 of the experiment. Feeding with indole-3-carbinole (I3C; 0.3% in rat chow), a natural xenobiotic which activates the Cyp1a1 promoter of the mouse Ren-2 gene, began on day 3 and lasted for 4 days until day 6. Systolic BP, body weight, plasma ANG II and tissue ANG II and ET-1 concentrations were determined daily. Severe hypertension developed as early as 1 day after beginning of I3C feeding which was accompanied by a significant reduction in body weight and by increases in plasma and tissue ANG II and left ventricle ET-1 concentrations. Atrasentan or bosentan had no effects on the rise in BP or plasma and tissue ANG II concentrations but prevented the rise in heart ventricle ET-1 concentration. Our data show that blockade of the ET system does not prevent or attenuate the rapid development of severe hypertension in iTGR; a long-term protective effect of ET blockade on cardiac (and renal) damage, however, cannot be excluded and awaits further investigations.
Journal: Vascular Pharmacology - Volume 50, Issues 5–6, May–June 2009, Pages 194–199