[Non-hypertensive desoxycorticosterone treatment enhances the progression of atherosclerosis in WHHL rabbit].
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.
Villeneuve
N
N
Institut de Recherches Servier, Suresnes.
Janiak
P
P
Brunel-Jacquemin
C
C
Canovi
C
C
Pillon
A
A
Breugnot
C
C
Gransagne
D
D
Vilaine
J P
JP
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006949:Hyperlipidemias / Q000378:metabolism*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D017366:Serotonin Receptor Agonists; D014280:Triglycerides; D012701:Serotonin; D003900:Desoxycorticosterone; D002784:Cholesterol
La déoxycorticostérone à dose non hypertensive accélère la progression de l'athérosclérose chez le lapin WHHL.