Effect of angiotensin II and enalapril on transfer of low-density lipoprotein into aortic intima in rabbits.
To assess the mechanism behind a possible atherosclerosis-promoting effect of angiotensin II, the influence of angiotensin II, noradrenaline, and enalapril on transfer of low-density lipoprotein (LDL) into the arterial wall was investigated in conscious rabbits. Intravascular infusion of angiotensin II (1.4 micrograms/kg per minute) initially increased the mean blood pressure from 70 to 80 mm Hg to 125 to 150 mm Hg; this effect was transient, and the blood pressure returned to baseline values within 2 hours, despite continuous infusion of angiotensin II. The normalized influx of LDL into the aortic intima, determined after in vivo exposure to 125I-LDL for 1 hour, was 88 +/- 17 (n = 6), 12 +/- 12 (n = 5), and 28 +/- 6 (n = 5) nL/cm2 per hour (mean +/- SEM) during angiotensin II infusion at high blood pressure, during angiotensin II infusion after the blood pressure had been normalized, and during continuous saline infusions, respectively (P < .05 for high blood pressure versus low blood pressure and saline). When noradrenaline was used to increase blood pressure to a level similar to that induced by angiotensin II, the normalized influx of LDL in noradrenaline-treated rabbits was also increased markedly. Production of endogenous angiotensin II was inhibited with enalapril (2.9 mg/kg per day). Compared with placebo rabbits, enalapril-treated rabbits had a 92% lower plasma angiotensin-converting enzyme activity and a 23% lower blood pressure. The normalized influx of LDL, however, was similar in the two groups at 18 +/- 2 (n = 10) and 20 +/- 3 (n = 10) nL/cm2 per hour, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
L B
LB
Nielsen
S
S
Stender
K
K
Kjeldsen
B G
BG
Nordestgaard
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D004656:Enalapril / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D017539:Tunica Intima / Q000378:metabolism*
D008077:Lipoproteins, LDL; D000804:Angiotensin II; D004656:Enalapril; D009638:Norepinephrine