Angiotensin II infusion increases hepatic triglyceride production via its type 2 receptor in rats.
OBJECTIVE
We recently reported that chronic angiotensin II (AII) infusion increases plasma triglyceride (TG) levels by stimulating hepatic TG production in rats. To explore this mechanism, we examined the roles of AII type 1 and type 2 receptors in TG metabolism in the same rat model.


RESULTS
Normal rats were infused continuously with AII (100 ng/kg per min) (n = 35) or vehicle (saline, n = 15) through an osmotic mini-pump for 2 weeks. The AII-infused rats were given drinking water with or without 0.01% olmesartan, an AII type 1 receptor (AT1R) blocker. AII infusion markedly elevated both the systolic and diastolic blood pressure, doubled the plasma levels of free fatty acid (FFA) and the TG secretion rate (TGSR), and increased the liver TG content by 37%. Olmesartan restored the blood pressure to normal as expected, but it exerted no effect in suppressing AII-induced hyper-TG or -FFA. Conversely, simultaneous infusion of PD123319, an AII type 2 receptor (AT2R) blocker, completely attenuated AII-induced TG production and thereby normalized the plasma TG and FFA levels. The infusion of CGP42112A, an AT2R agonist, increased plasma FFA and TG levels by 47 and 32%, respectively, in normal rats. CGP42112A also increased TGSR by 33% and the liver TG content by 61%. Plasma FFA levels were significantly correlated with TGSR (r = 0.45, P < 0.05).


CONCLUSIONS
These results suggest, first, that AII stimulates hepatic TG production via the action of AT2R, and second, that this TG overproduction might be attributable to increased FFA flux into the liver.
First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Jianmin
J
Ran
Tsutomu
T
Hirano
Mitsuru
M
Adachi
D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology; D008099:Liver / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists*; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D014280:Triglycerides / Q000096:biosynthesis* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D005230:Fatty Acids, Nonesterified; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; C437965:olmesartan