Coexistence of
hypertension and
lipid disorders enhances the development of
atherosclerosis. However it is still unclear whether this promoting effect of
hypertension results only from hemodynamic changes or whether part of it is mediated by humoral or neurogenic factors independently of blood pressure alteration. The aim of this study is to determine whether
mineralocorticoids, which are known to be involved in the pathogenesis of
hypertension, can influence the atherosclerotic process in Watanabe heritable hyperlipidemic rabbits (WHHL) independently of pressure changes. For this purpose,
DOCA (200 or 400 mg/kg) or vehicle were implanted subcutaneously for 4 weeks in 3 months old WHHL or New Zealand (NZ) rabbits, without
nephrectomy and with a fluid intake
solution of 1% NaCl +0.2% KCl.
DOCA treatment, independently of hemodynamic changes, significantly increases the size of atherosclerotic lesions in parallel with the aortic
cholesterol esters content in the arch and thoracic aorta of WHHL rabbits. Plasmatic and aortic
cholesterol and
triglyceride content remains unchanged by
DOCA treatment. Alteration of endothelial function usually found in WHHL rabbits is accentuated 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 which are implicated also in
atherogenesis and support the clinical observations that a reduction of arterial pressure in hypertensive atherosclerotic patients is not sufficient to reduce the progression of this
vascular disease.