Inhibition of angiotensin II-induced contraction by losartan in human coronary arteries.
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.
Department of Internal Medicine, Lund University Hospital, Sweden.
A
A
Holmgren
E
E
Pantev
D
D
Erlinge
L
L
Edvinsson
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019808:Losartan