Effect of deoxycorticosterone acetate on blood pressure in relation to accumulation of low-density lipoprotein and fibrinogen by aorta and other tissues of normotensive Wistar rats.
OBJECTIVE
To evaluate the effect of different 4-week doses of deoxycorticosterone acetate (DOCA), together with 0.9% sodium chloride in the drinking water (DOCA-salt) on the blood pressure and on the accumulation of low-density lipoprotein (LDL) and fibrinogen in artery walls ad other tissues in conscious, unrestrained, normotensive Wistar-Kyoto rats.


METHODS
The accumulation of LDL labelled with 125I via the adduct tyramine cellobiose ([125I]-TC-LDL) and of fibrinogen similarly labelled with 131I ([131I]-TC-fibrinogen) was compared in aortic walls, heart, liver, kidney, lung. skeletal muscle, and adrenal gland tissues during the final 24 h of a 4-week administration of DOCA-salt, with vehicle-salt and saline as controls.


RESULTS
In control and vehicle rats the blood pressure did not change significantly during the last 5 days of treatment. Administration of DOCA-salt produced a dose-dependent increase in blood pressure during the same period. DOCA-salt administration increased LDL accumulation in the aorta and the heart and decreased LDL accumulation in the adrenal gland compared with those in rats of the control and vehicle groups. DOCA-salt administration did not affect fibrinogen accumulation significantly.


CONCLUSIONS
DOCA-salt treatment produces an increase in arterial blood pressure accompanied by an increase in LDL accumulation by the aortic wall and heart and a decrease in LDL accumulation by the adrenal gland. These observations raise the possibility that one mechanism by which hypertension affects atherosclerosis is through increased LDL accumulation in arterial walls.
Medina
R A
RA
Pathopharmacology Unit, William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, UK.
Cardona-Sanclemente
L E
LE
Born
G V
GV
Brown
M J
MJ
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone / Q000633:toxicity*; D005340:Fibrinogen / Q000378:metabolism*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D012982:Sodium, Dietary / Q000008:administration & dosage; D014018:Tissue Distribution
D008077:Lipoproteins, LDL; D012982:Sodium, Dietary; D003900:Desoxycorticosterone; D005340:Fibrinogen