Inhibition of angiotensin II-induced contraction by losartan in human coronary arteries

J Cardiovasc Pharmacol. 1998 Oct;32(4):662-4. doi: 10.1097/00005344-199810000-00021.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / antagonists & inhibitors
  • Angiotensin II / pharmacology*
  • Angiotensin Receptor Antagonists*
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology*
  • Coronary Vessels / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Losartan / administration & dosage
  • Losartan / pharmacology*
  • Muscle Contraction / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • Vasoconstrictor Agents / antagonists & inhibitors
  • Vasoconstrictor Agents / pharmacology*

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Vasoconstrictor Agents
  • Angiotensin II
  • Losartan