Functional antagonism of different angiotensin II type I receptor blockers in human arteries.

Abstract:

OBJECTIVES:To evaluate and compare the functional type and the degree of antagonism of the selective angiotensin II type 1 receptor blockers (ARB) losartan, EXP 3174 (the active metabolite of losartan), valsartan and candesartan in human internal mammary arteries. METHODS:Human internal mammary arteries were obtained as excess graft material during coronary bypass surgery. Vessels were prepared as rings and mounted in an organ bath in which vasoconstriction and -dilation can be measured. Concentration-response curves of angiotensin II-mediated vasoconstriction were measured in absence or presence of different concentrations of one of the ARBs. RESULTS:Losartan showed a rightward shift of the angiotensin II-mediated vasoconstriction, whereas addition of its metabolite EXP 3174 caused a decrease of the maximal effect of angiotensin II. Incubation with valsartan and candesartan also resulted in a decrease of the maximal effect. The inhibiting effects on the angiotensin II-mediated vasoconstriction by the highest concentration of EXP 3174, valsartan and candesartan did not differ significantly. CONCLUSION:In human internal mammary arteries, losartan acts as a surmountable antagonist. On the other hand, EXP 3174, valsartan and candesartan demonstrate an insurmountable type of antagonism. Furthermore, the inhibiting effects of EXP 3174, valsartan and candesartan in our study are equal in the highest concentrations.

journal_name

Cardiovasc Drugs Ther

authors

Wagenaar LJ,Voors AA,Buikema H,van Buiten A,Lübeck RH,Boonstra PW,van Veldhuisen DJ,van Gilst WH

doi

10.1023/a:1021729909456

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

311-6

issue

4

eissn

0920-3206

issn

1573-7241

pii

5109067

journal_volume

16

pub_type

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