Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension.
Right ventricular myocardial hypertrophy during hypoxic pulmonary hypertension is associated with local renin-angiotensin system activation. The expression of angiotensin II type 1 (AT(1)) and type 2 (AT(2)) receptors in this setting has never been investigated. We have therefore examined the chronic hypoxia pattern of AT(1) and AT(2) expression in the right and left cardiac ventricles, using in situ binding and RT-PCR assays. Hypoxia produced right, but not left, ventricular hypertrophy after 7, 14, and 21 days, respectively. Hypoxia for 2 days was associated in each ventricle with a simultaneous and transient increase (P < 0.05) in AT(1) binding and AT(1) mRNA levels in the absence of any significant change in AT(2) expression level. Only after 14 days of hypoxia, AT(2) binding increased (P < 0.05) in the two ventricles, concomitantly with a right ventricular decrease (P < 0.05) in AT(2) mRNA. Along these data, AT(1) and AT(2) binding remained unchanged in both the left and hypertrophied right ventricles from rats treated with monocrotaline for 30 days. These results indicate that chronic hypoxia induces modulations of AT(1) and AT(2) receptors in both cardiac ventricles probably through direct and indirect mechanisms, respectively, which modulations may participate in myogenic (at the level of smooth or striated myocytes) rather than in the growth response of the heart to hypoxia.
Institut National de la Santé et de la Recherche Médicale (INSERM) U127/572, Institut Fédératif de Recherche Circulation Paris VII, Hôpital Lariboisière, Université Denis Diderot, 41 boulevard de la Chapelle, 75475 Paris cedex 10, France.
Christophe
C
Adamy
Patricia
P
Oliviero
Saadia
S
Eddahibi
Lydie
L
Rappaport
Jane-Lise
JL
Samuel
Emmanuel
E
Teiger
Catherine
C
Chassagne
D000818:Animals; D006352:Heart Ventricles; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000473:pathology; D000860:Hypoxia / Q000150:complications*; D008024:Ligands; D008297:Male; D016686:Monocrotaline; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*
D008024:Ligands; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D016686:Monocrotaline