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Comparison of the Inhibitory Actions of Angiotensin AT1 Receptor Antagonists in the Peripheral Vascular Bed

  • Hunter C. Champion
  • David G. Lambert
  • Trinity J. Bivalacqua
  • Dennis B. Mcnamara
  • Philip J. Kadowitz
Part of the Progress in Experimental Cardiology book series (PREC, volume 2)

Summary

The effects of nonpeptide angiotensin AT1 and AT2 receptor antagonists on pressor responses to the angiotensin peptides were investigated in the cat and the rat. Under constant flow conditions, injections of angiotensin (Ang) I, Ang II, Ang III, Ang I-(3-10), (Pro11,D-Ala12) Ang I and Ang IV into the hindlimb perfusion circuit caused dose-dependent increases in perfusion pressure, while Ang I-(4-8) was without effect. The order of potency was Ang I = Ang II = Ang III > (Pro11,D-Ala12) Ang I > Ang I-(3-10) = Ang IV. Losartan, EXP 3174, and candesartan decreased vasoconstrictor responses to Ang II in a selective manner. EXP 3174 (1 mg/kg iv) and candesartan (1 mg/kg iv) shifted the dose-response curve to Ang II to the right in a nonparallel manner, whereas losartan shifted the curve to the right in a parallel manner. The AT2 receptor antagonist PD 123,319 had no significant effect on vasoconstrictor responses to the angiotensin peptides in the regional vascular bed of the cat. In the rat, candesartan decreased pressor responses to Ang II, whereas PD 123,319 had no effect on the response to the peptide. These results indicate that vasoconstrictor responses to Ang peptides in the regional vascular bed of the cat and pressor responses to Ang II in the systemic vascular bed of the rat are mediated by the activation of AT1 receptors, whereas AT2 receptors play little, if any, role in the mediation or modulation of responses to Ang II in the cat or the rat.

Keywords

Systemic Arterial Pressure Angiotensin Peptide Nonpeptide Angiotensin Nonparallel Manner Full Intrinsic Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Hunter C. Champion
    • 1
  • David G. Lambert
    • 1
  • Trinity J. Bivalacqua
    • 1
  • Dennis B. Mcnamara
    • 1
  • Philip J. Kadowitz
    • 1
  1. 1.Tulane University School of MedicineNew OrleansUSA

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