RESPECTIVE ROLE OF HUMORAL-FACTORS AND BLOOD-PRESSURE IN AORTIC REMODELING OF DOCA HYPERTENSIVE RATS

Hypertension results in increased thickness and stiffness of large art ery walls. The goal of our study was to assess the respective roles of humoral factors such as Ang II, endothelin and blood pressure in thes e aortic modifications. For this purpose, uninephrectomized rats recei ved DOCA and high salt diet, and when hypertension was installed, they were treated for 5 weeks with either a long-acting calcium antagonist , mibefradil (30 mg/kg/day), an ACE inhibitor, enalapril (3 mg/kg/day) , or a mixed ET(A) and ET(B) endothelin receptor antagonist, bosentan (100 mg/kg/day). A group of hypertensive rats was left untreated and a sham-operated group of normotensive rats was used for control. At the end of treatment, aortic medial thickness and elastin as well as coll agen were evaluated by quantitative morphometry. DOCA-salt hypertensiv e rats exhibited a marked increase in medial thickness associated with no change in absolute content in extracellular matrix. Elastin relati ve density decreased in DOCA rats. Enalapril had no effect on arterial pressure. Bosentan decreased slightly (by 12 mm Hg), but not signific antly, blood pressure. None of these drugs had an effect on medial thi ckness suggesting that in DOCA hypertensive rats neither Ang II nor en dothelin play a significant role in the remodeling of the aorta. In co ntrast, mibefradil almost normalized arterial pressure, prevented medi al hypertrophy and increased elastin density. Further studies are requ ired in order to assess if this effect is directly linked to the blood pressure decrease or to another mechanism related to the calcium anta gonistic property of mibefradil.