Inhibition of Angiotensin II-Induced Contraction by Losartan in Human Coronary Arteries

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Abstract

Summary:

The in vitro effects of angiotensin II (Ang II) in human vessels are not well studied. The development of specific Ang II-receptor antagonists has made it possible to delineate more carefully the receptor mechanisms involved. The objective of this study was twofold: to investigate the effect of Ang II on human coronary arteries and to study the effects of angiotensin II type 1 receptor blockade with losartan. The setting was contractile experiments with ring segments of coronary arteries. We observed that Ang II is a vasoconstrictor of human coronary arteries, with a pEC50 value of 9.26 ± 0.22 and Emax of 68.7 ± 9.61% of potassium-induced contraction. Losartan (10-100 nM) shifted the concentration-response curve of Ang II to the right, with pEC50 values of 7.64 ± 0.10 and 7.00 ± 0.15, respectively (p = 0.001), demonstrating the antagonistic properties of losartan. We also noted a decreased maximal response to Ang II after incubation of losartan, with Emax of 51.1 ± 7.08% and 41.9 ± 4.70% (p = 0.05), respectively. In conclusion, this is the first report describing the contractile effect of Ang II and the antagonizing effects of losartan in isolated human coronary arteries.

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