EFFECT OF NONHYPERTENSIVE DOCA-SALT TREAT MENT ON ATHEROGENESIS IN WHHL RABBIT

Coexistence of hypertension and lipid disorders enhances the developme nt of atherosclerosis. However it is still unclear whether this promot ing effect of hypertension results only from hemodynamic changes or wh ether part of it is mediated by humoral or neurogenic factors independ ently of blood pressure alteration. The aim of this study is to determ ine whether mineralocorticoids, which are known to be involved in the pathogenesis of hypertension, can influence the atherosclerotic proces s in Watanabe heritable hyperlipidemic rabbits (WHHL) independently of pressure changes. For this purpose, DOCA (200 or 400 mg/kg) or vehicl e were implanted subcutaneously for 4 weeks in 3 months old WHHL or Ne w Zealand (NZ) rabbits, without nephrectomy and with a fluid intake so lution of 1 % NaCl +0.2 % KCl. DOCA treatment, independently of hemody namic changes, significantly increases the size of atherosclerotic les ions in parallel with the aortic cholesterol esters content in the arc h and thoracic aorta of WHHL rabbits. Plasmatic and aortic cholesterol and triglyceride content remains unchanged by DOCA treatment. Alterat ion of endothelial function usually found in WHHL rabbits is accentuat ed only for the dose of 400 mg/kg. Aortic sensitivity to serotonin is not altered, but the maximal contraction to this agonist is decreased in both strains by mineralocorticoid treatment. These results indicate the importance of non-hemodynamic factors related to hypertension whi ch are implicated also in atherogenesis and support the clinical obser vations that a reduction of arterial pressure in hypertensive atherosc lerotic patients is not sufficient to reduce the progression of this v ascular disease.