[Cardiac and vascular hypertrophy in hypertension due to angiotensin II. Effect of losartan and bosentan].
We assessed the role of angiotensin (Ang) II type 1 receptor (AT1) and endothelin type A and B (ETA & ETB) receptor in cardiovascular hypertrophy associated with angiotensin II-induced hypertension (200 ng/kg.min s.c. for 10 or 17 days). Antagonism of AT1 receptors was obtained by oral administration of losartan (10 or 30 mg/kg.day) and blockade of ETA and ETB receptors was obtained by oral administration of bosentan (30 mg/kg.day). Losartan and bosentan were administered 24 h before and during the 10 days of angiotensin II (prevention) or they were given after the development of hypertension i.e. from day 10 to 17 of angiotensin II (treatment). Tail-cuff pressure (TCP) was measured before and at the end of the period of administration of antagonists. At the end of experiments, cross sectional area (CSA, mm2) of the carotid was measured after perfusion and fixation at 100 mmHg and heart weight index (HWI, mg/g body weight) was determined. Results are mean +/- SEM. [table: see text] In addition to its blood pressure lowering effect, both doses of losartan prevented and reversed the cardiovascular hypertrophy induced by angiotensin II. Similarly, bosentan prevented and reversed the effect of angiotensin II on cardiovascular structure independently of arterial pressure. These results indicate that the effect of angiotensin II on blood pressure, heart and carotid structure is exclusively mediated by AT1 receptors. The influence of bosentan suggests that endothelin plays an important role in local action of angiotensin II independently of blood pressure level.
Herizi
A
A
Institut universitaire de recherche clinique, Groupe rein et hypertension, Montpellier.
Belabbas
H
H
Mimran
A
A
Jover
B
B
D000704:Analysis of Variance; D000804:Angiotensin II / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D000077300:Bosentan; D006332:Cardiomegaly / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors; D005500:Follow-Up Studies; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy; D006984:Hypertrophy; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D000804:Angiotensin II; D019808:Losartan; D000077300:Bosentan