Comparison of the effects of AT1 receptor blockade and angiotensin converting enzyme inhibition on atherosclerosis.

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Hope S, Brecher P, Chobanian AV

Comparison of the effects of AT1 receptor blockade and angiotensin converting enzyme inhibition on atherosclerosis.

Am J Hypertens. 1999 Jan;12(1 Pt 1):28-34.

PubMed ID

10075381 [ View in PubMed

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Abstract

Angiotensin converting enzyme (ACE) inhibitors reduce the development of atherosclerosis in hypercholesterolemic animals across a wide range of species. Although the mechanism for these effects has not been well delineated, it has been assumed generally that both angiotensin II suppression and interference with the breakdown of bradykinin are involved. To determine whether angiotensin II receptor blockade provides similar effects as those observed with ACE inhibition, we examined the influence of irbesartan, an AT1 receptor antagonist, on aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits using the identical protocol that was employed in our earlier studies involving ACE inhibitors. At a dose of irbesartan (30 mg/kg/day), which was selected because it appeared to block most of the pressor effects of infused angiotensin in rabbits, no effect on atherosclerosis was observed. However, a higher dose of irbesartan (75 mg/kg/day) caused reductions in blood pressure and aortic atherosclerosis similar to those seen in earlier studies with ACE inhibitors. The decrease in aortic intimal surface involvement with irbesartan was from 38.9 +/- 3.8% in controls to 24.1 +/- 3.0% in the treated group (P < .01). Aortic cholesterol content was also significantly reduced in those animals (P < .02). The findings indicate that suppression of the renin-angiotensin system by AT1 receptor blockade in a genetically hypercholesterolemic rabbit model causes comparable inhibition of aortic atherosclerosis as that achieved by ACE inhibition, and that a mild reduction of blood pressure induced by both classes of agents may contribute to their antiatherosclerotic action in this model.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Irbesartan	Type-1 angiotensin II receptor	Protein	Humans	Yes	Antagonist	Details