title: Endothelin receptor blockade does not affect blood pressure or angiotensin II levels in CYP1A1-Ren-2 transgenic rats with acutely induced hypertension.
abstract: We found previously that selective blockade of endothelin ETA receptors is superior to nonselective ET(A)/ET(B) 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 ET(A)/ET(B), or with atrasentan, a selective ET(A) receptor blocker, was started on day 2 of the experiment. Feeding with indole-3-carbinole (13C; 03% in rat chow), a natural xenobiotic which activates the Cyplal 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 13C 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.
authors: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors: Zdenka
authors: Z
authors: Vanourková
authors: Herbert J
authors: HJ
authors: Kramer
authors: Michaela
authors: M
authors: Erbanová
authors: Angela
authors: A
authors: Bäcker
authors: Ludek
authors: L
authors: Cervenka
authors: Zuzana
authors: Z
authors: Husková
authors: Vera Certíková
authors: VC
authors: Chábová
authors: Vladimír
authors: V
authors: Tesar
authors: Pavel
authors: P
authors: Dvorák
authors: Jan
authors: J
authors: Malý
authors: Ivana
authors: I
authors: Vanecková
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000077868:Atrasentan; D001794:Blood Pressure / Q000187:drug effects*; D000077300:Bosentan; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000235:genetics*; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D006352:Heart Ventricles / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy*; D007211:Indoles / Q000009:adverse effects; D007668:Kidney / Q000378:metabolism; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007211:Indoles; D011759:Pyrrolidines; C535029:Ren2 protein, rat; D013449:Sulfonamides; D000804:Angiotensin II; C016517:indole-3-carbinol; D019363:Cytochrome P-450 CYP1A1; D012083:Renin; D000077300:Bosentan; D000077868:Atrasentan