Guinea pig airway hyperresponsiveness induced by blockade of the angiotensin II type 1 receptor. Role for endogenous nitric oxide

American Journal of Respiratory and Critical Care Medicine
H KanazawaJ Yoshikawa

Abstract

Losartan is the first angiotensin II type 1 (AT1) receptor antagonist to become available for the treatment of hypertension. However, recent reports have revealed several cases of losartan-induced bronchoconstriction. We investigated to determine the mechanism of losartan-induced bronchoconstriction, considering in particular the involvement of endogenous nitric oxide (NO). In this study, we examined the effects of losartan on airway obstruction and endogenous NO production using anesthetized guinea pigs and cultured airway epithelial cells. Five minutes after administration of angiotensin II (Ang II), the bronchoconstriction induced by acetylcholine was not changed. In contrast, Ang II in the presence of losartan caused a significant increase in the acetylcholine responsiveness. Pretreatment with L-N omega-nitroarginine-methylester (L-NAME) potentiated acetylcholine-induced bronchoconstriction 5 min after administration of Ang II, and L-arginine reversed this action of L-NAME on the acetylcholine responsiveness. Moreover, Ang II administration increased NO concentration in expired air (12.5 +/- 1.5 ppb for saline, 40 +/- 5 ppb for Ang II, p < 0.01), and losartan significantly inhibited Ang II-stimulated NO release (20 +/- 3.5 ...Continue Reading

References

Mar 25, 1991·European Journal of Pharmacology·M Entzeroth, S Hadamovsky
Dec 10, 1985·European Journal of Pharmacology·G Folkerts, F P Nijkamp
Jan 1, 1973·Respiration; International Review of Thoracic Diseases·B G SimonssonN Svedmyr
Dec 7, 1995·The New England Journal of Medicine·C G Acker, A Greenberg
Jan 1, 1995·The Journal of Clinical Investigation·G FolkertsF P Nijkamp
Jun 15, 1993·Biochemical and Biophysical Research Communications·H TsukaharaM S Goligorsky
Dec 1, 1996·The Journal of Allergy and Clinical Immunology·P V DicpinigaitisD L Rosenstreich
Feb 1, 1997·American Journal of Respiratory and Critical Care Medicine·H KanazawaJ Yoshikawa

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Citations

Jun 7, 2000·The Journal of Clinical Investigation·S EddahibiS Adnot

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