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Effect of infused angiotensin II on the bronchoconstrictor activity of inhaled endothelin-1 in asthma.
Chest. 1999 Feb; 115(2):352-6.Chest

Abstract

STUDY OBJECTIVES

Endothelin (ET)-1 is a potent bronchoconstrictor, and asthmatics demonstrate bronchial hyperresponsiveness to ET-1 given by inhalation. Angiotensin II (Ang II) is increased in plasma in acute severe asthma, causes bronchoconstriction in asthmatics, and potentiates contractions induced by ET-1 in bovine bronchial smooth muscle in vitro, and contractions induced by methacholine both in vitro and in vivo. We wished to examine any potentiation of the bronchoconstrictor activity of inhaled ET-1 by infused Ang II at subbronchoconstrictor doses.

DESIGN

Double-blind randomized placebo-controlled study.

SETTING

Asthma research unit in university hospital.

PATIENTS

Eight asthmatic subjects with baseline FEV1 88% predicted, bronchial hyperreactivity (geometric mean, concentration of methacholine producing 20% fall, methacholine PC20 2.5 mg/mL), and mean age 37.1 years.

INTERVENTIONS

We examined the effect of subbronchoconstrictor doses of infused Ang II (1 ng/kg/min and 2 ng/kg/min) or placebo on bronchoconstrictor responses to inhaled ET-1 (dose range, 0.96 to 15.36 nmol).

MEASUREMENTS

Oxygen saturation, noninvasive BP, and spirometric measurements were made throughout the study visits. Blood was sampled for plasma Ang II levels at baseline and before and after ET-1 inhalation.

RESULTS

Ang II infusion did not produce bronchoconstriction per se at either dose prior to ET-1 challenge. Bronchial challenge with inhaled ET-1 produced dose-dependent bronchoconstriction, but there was no difference in bronchial responsiveness to ET-1 comparing infusion of placebo with Ang II at 1 ng/kg/min or 2 ng/kg/min (geometric mean, concentration of ET-1 producing 15% fall, 5.34 nmol, 4.95 nmol, and 4.96 nmol, respectively) (analysis of variance, p > 0.05). There was an increase in systolic and diastolic BP at the higher dose of Ang II compared to placebo (mean 136/86 vs 117/75 mm Hg, respectively). Plasma Ang II was elevated following infusion of both doses of Ang II compared to placebo.

CONCLUSIONS

In contrast to the potentiating effect on methacholine-induced bronchoconstriction, Ang II at subbronchoconstrictor doses does not potentiate ET-1-induced bronchoconstriction in asthma.

Authors+Show Affiliations

Department of Respiratory Medicine, West Glasgow Hospitals University NHS Trust, Scotland, UK. gchalmers@btinternet.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10027431

Citation

Chalmers, G W., et al. "Effect of Infused Angiotensin II On the Bronchoconstrictor Activity of Inhaled Endothelin-1 in Asthma." Chest, vol. 115, no. 2, 1999, pp. 352-6.
Chalmers GW, Millar EA, Little SA, et al. Effect of infused angiotensin II on the bronchoconstrictor activity of inhaled endothelin-1 in asthma. Chest. 1999;115(2):352-6.
Chalmers, G. W., Millar, E. A., Little, S. A., Shepherd, M. C., & Thomson, N. C. (1999). Effect of infused angiotensin II on the bronchoconstrictor activity of inhaled endothelin-1 in asthma. Chest, 115(2), 352-6.
Chalmers GW, et al. Effect of Infused Angiotensin II On the Bronchoconstrictor Activity of Inhaled Endothelin-1 in Asthma. Chest. 1999;115(2):352-6. PubMed PMID: 10027431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of infused angiotensin II on the bronchoconstrictor activity of inhaled endothelin-1 in asthma. AU - Chalmers,G W, AU - Millar,E A, AU - Little,S A, AU - Shepherd,M C, AU - Thomson,N C, PY - 1999/2/23/pubmed PY - 1999/2/23/medline PY - 1999/2/23/entrez SP - 352 EP - 6 JF - Chest JO - Chest VL - 115 IS - 2 N2 - STUDY OBJECTIVES: Endothelin (ET)-1 is a potent bronchoconstrictor, and asthmatics demonstrate bronchial hyperresponsiveness to ET-1 given by inhalation. Angiotensin II (Ang II) is increased in plasma in acute severe asthma, causes bronchoconstriction in asthmatics, and potentiates contractions induced by ET-1 in bovine bronchial smooth muscle in vitro, and contractions induced by methacholine both in vitro and in vivo. We wished to examine any potentiation of the bronchoconstrictor activity of inhaled ET-1 by infused Ang II at subbronchoconstrictor doses. DESIGN: Double-blind randomized placebo-controlled study. SETTING: Asthma research unit in university hospital. PATIENTS: Eight asthmatic subjects with baseline FEV1 88% predicted, bronchial hyperreactivity (geometric mean, concentration of methacholine producing 20% fall, methacholine PC20 2.5 mg/mL), and mean age 37.1 years. INTERVENTIONS: We examined the effect of subbronchoconstrictor doses of infused Ang II (1 ng/kg/min and 2 ng/kg/min) or placebo on bronchoconstrictor responses to inhaled ET-1 (dose range, 0.96 to 15.36 nmol). MEASUREMENTS: Oxygen saturation, noninvasive BP, and spirometric measurements were made throughout the study visits. Blood was sampled for plasma Ang II levels at baseline and before and after ET-1 inhalation. RESULTS: Ang II infusion did not produce bronchoconstriction per se at either dose prior to ET-1 challenge. Bronchial challenge with inhaled ET-1 produced dose-dependent bronchoconstriction, but there was no difference in bronchial responsiveness to ET-1 comparing infusion of placebo with Ang II at 1 ng/kg/min or 2 ng/kg/min (geometric mean, concentration of ET-1 producing 15% fall, 5.34 nmol, 4.95 nmol, and 4.96 nmol, respectively) (analysis of variance, p > 0.05). There was an increase in systolic and diastolic BP at the higher dose of Ang II compared to placebo (mean 136/86 vs 117/75 mm Hg, respectively). Plasma Ang II was elevated following infusion of both doses of Ang II compared to placebo. CONCLUSIONS: In contrast to the potentiating effect on methacholine-induced bronchoconstriction, Ang II at subbronchoconstrictor doses does not potentiate ET-1-induced bronchoconstriction in asthma. SN - 0012-3692 UR - https://www.unboundmedicine.com/medline/citation/10027431/Effect_of_infused_angiotensin_II_on_the_bronchoconstrictor_activity_of_inhaled_endothelin_1_in_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-3692(15)50575-8 DB - PRIME DP - Unbound Medicine ER -