Tone-dependent responses to acetylcholine in the feline pulmonary vascular bed

The effects of an increase in base-line tone on pulmonary vascular responses to acetylcholine were investigated in the pulmonary vascular bed of the intact-chest cat. Under conditions of controlled blood flow and constant left atrial pressure, intralobar injections of acetylcholine under low-tone base-line conditions increased lobar arterial pressure in a dose-related manner. When tone was increased moderately by alveolar hypoxia, acetylcholine elicited dose-dependent decreases in lobar arterial pressure, and at the highest dose studied, acetylcholine produced a biphasic response. When tone was raised to a high steady level with the prostaglandin analogue, U46619, acetylcholine elicited marked dose-related decreases in lobar arterial pressure. Atropine blocked both vasoconstrictor responses at low tone and vasodilator responses at high tone, whereas meclofenamate and BW 755C had no effect on responses to acetylcholine at low or high tone. The vasoconstrictor response at low tone was blocked by pirenzepine (20 and 50 micrograms/kg iv) but not gallamine (10 mg/kg iv). The vasodilator response at high tone was not blocked by pirenzepine (50 micrograms/kg iv) or gallamine or pancuronium (10 mg/kg iv). The present data support the concept that pulmonary vascular responses to acetylcholine are tone dependent and suggest that the vasoconstrictor response under low-tone conditions is mediated by a high-affinity muscarinic (M1)-type receptor. These data also suggest that vasodilator responses under high-tone conditions are mediated by muscarinic receptors that are neither M1 nor M2 low-affinity muscarinic-type receptor and that responses to acetylcholine are not dependent on the release of cyclooxygenase or lipoxygenase products.