Effect of captopril and losartan on blood pressure and accumulation of LDL and fibrinogen by aortic wall and other tissues in normotensive and hypertensive rats.
Hypertension, low-density lipoprotein (LDL), and fibrinogen are risk factors for atherosclerosis. We investigated the effect of reducing blood pressure, by blocking the renin-angiotensin system (RAS), on the accumulation of these atherogenic proteins in arterial walls and other tissues in conscious, unrestrained, normotensive and hypertensive rats. The accumulation of LDL and fibrinogen, labeled respectively with 125I and 131I via the adduct tyramine cellobiose ([125I]-TC-LDL and [131I]-TC-fibrinogen) was compared in aortic walls, heart, lung, skeletal muscle, liver, kidney, and adrenal gland during the final 24 h of treatment with either the angiotensin-converting enzyme (ACE) inhibitor captopril or the angiotensin II-receptor I (AT1) antagonist losartan. In normotensive rats, the blood pressure was decreased only by losartan. In spontaneously hypertensive rats (SHRs), the blood pressure was decreased by both losartan and captopril. Captopril had no significant effect on the accumulation of LDL or fibrinogen by the aortic wall. Losartan significantly increased the accumulation of LDL by the aortic wall of SHRs. Neither agent produced any change in LDL or fibrinogen accumulation in any of the other tissues. These results indicate that although blocking the RAS at either the enzymic or receptor level produces significant decrease of blood pressure in hypertensive animals, only losartan has any affect on LDL accumulation by the aortic wall.
Medina
R
R
Pathopharmacology Unit, William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, England, U.K.
Cardona-Sanclemente
L E
LE
Born
G V
GV
Brown
M J
MJ
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D005340:Fibrinogen / Q000032:analysis / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D019808:Losartan; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D008077:Lipoproteins, LDL; D013777:Tetrazoles; D005340:Fibrinogen; D002216:Captopril; D019808:Losartan