Protective effect of urodilatin (URO) or ANP against an acetylcholine(ACH)-induced bronchoconstriction in the rat in vivo: Abstract

Inhaled ANP inhibits histamine induced bronchoconstriction in man. We compared the protective effect of equimolar doses of intravenous ANP and URO against a bronchoconstriction induced by ACH-inhalation in 46 anaesthetized intubated spontaneously breathing Wistar-rats. The animals received an intravenous infusion of 0.5 ml ANP, URO or vehicle (NaCl) for 10 min. During the infusion period an ACH-challenge test was started after 5 min. Using whole-bodyplethysmography typical spontaneous respiratory function parameters were recorded under steady state conditions before the infusion and before and at the of the ACH-challenge. Forced parameters (volume-time and flow-volume relation) were measured in hyperventilation-induced apnoe after the ACH-challenge and included e.g. FVC, FEV0.1, FEV0.2, PEF, MMEF, FEF75, FEF50 and FEF25. ACH induced a significant bronchoconstriction without any significant difference between the treatment groups regarding the spontaneous breathing and forced volume-time relation parameters. The more sensitive flow-volume curve, however, showed a significant protective effect of 11.4 and 22.8 pmol/kg/min (40 and 80 ng/kg/min) URO compared to the control group while the infusion of ANP was without any significant influence in all three dose groups. Heart rate was controlled by ECG and did not change significantly during the infusion period before and at the end of the ACH-challenge. It is concluded that intravenous URO but not ANP shows a significant protective effect against ACH-induced bronchoconstriction in rats in vivo