Non-hypertensive deoxycorticosterone-salt treatment accelerates atherosclerosis progression in Watanabe heritable hyperlipidemic rabbit.
Epidemiological studies have indicated that hypertension enhances the development of atherosclerosis in patients with lipid disorders. However, it was still unclear whether this promoting effect resulted only from hemodynamic changes or whether part of it was mediated by humoral or neurogenic factors independent of blood pressure alteration. The aim of this study was to determine whether mineralocorticoids, which are known to be involved in the pathogenesis of hypertension, could be implicated in the atherosclerotic process independent of pressure changes. For this purpose, the effect of deoxycorticosterone (DOCA, 200 mg/kg s.c.) on aortic atherosclerosis was studied in Watanabe heritable hyperlipidemic (WHHL) rabbits in comparison with New Zealand rabbits. After 4 weeks of treatment, DOCA significantly increased the size of atherosclerotic lesions in the arch and thoracic aorta (+115%) in parallel with the aortic cholesterol ester content (+83%). The vascular free cholesterol and triglyceride content remained unchanged on DOCA treatment, as were arterial pressure and plasma cholesterol levels. None of these effects was observed in New Zealand rabbits. DOCA did not accentuate the alteration of endothelial function usually found in WHHL rabbits. The sensitivity to serotonin was not altered, but the maximal contraction to this agonist was decreased in both strains by mineralocorticoid treatment.
Janiak
P
P
Cardiovascular Division, Institut de Recherches Servier, Suresnes, France.
Villeneuve
N
N
Pillon
A
A
Jacquemin
C
C
Breugnot
C
C
Gransagne
D
D
Vilaine
J P
JP
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000032:analysis; D003900:Desoxycorticosterone / Q000494:pharmacology*; D005260:Female; D006949:Hyperlipidemias / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D011817:Rabbits; D014280:Triglycerides / Q000032:analysis
D014280:Triglycerides; D003900:Desoxycorticosterone; D002784:Cholesterol