Bronchoprotective and bronchodilator activity of anaritide (human atrial natriuretic factor [102-126]) infusion in the anesthetized guinea pig.
The present study examined the bronchoprotective and bronchodilator efficacy of infused human atrial natriuretic factor [102-126] (Anaritide) in the guinea pig. Anesthetized and paralyzed male guinea pigs, ventilated via a tracheal cannula, were placed in a plethysmograph for measurement of agonist-induced changes in pulmonary mechanics. Reductions in dynamic compliance of the lung and airway conductance were produced either by 3 to 7 tidal volume breaths of leukotriene D4 (0.125 micrograms/ml) delivered through an ultrasonic nebulizer or by intravenous histamine (2.8 +/- 0.2 micrograms/kg). Infusion of Anaritide (1 microgram/kg/min), before evoking bronchoconstriction with either LTD4 or histamine, produced a significant protection against bronchoconstriction produced by aerosol LTD4, but not against histamine-induced bronchoconstriction of similar magnitude. In other experiments, Anaritide infusion (0.5-2 micrograms/kg/min) also rapidly reversed a stable LTD4-induced decrease in airway conductance, but did not produce a similar reversal of the decrease in dynamic compliance. The data provide evidence that intravenous Anaritide exerts both bronchoprotective and bronchodilator effects against LTD4-induced bronchospasm.
Englebach
I M
IM
Wyeth-Ayerst Research, Princeton, NJ 08540.
Lappe
R W
RW
Hand
J M
JM
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001993:Bronchodilator Agents; C472955:NPPA protein, human; D010446:Peptide Fragments; D013189:SRS-A; C042703:anaritide; D009320:Atrial Natriuretic Factor