Effects of acetylcholine in the pulmonary circulation of rabbits.
The pulmonary and systemic vascular beds differ in their response to several vasoactive substances. Acetylcholine (ACh) is a potent systemic vasodilator; however, its effects on the pulmonary circulation are not clear. Utilizing the isolated rabbit lung preparation perfused in situ under constant flow (92 +/- 3 ml/min) with an albumin-enriched physiologic salt solution, we studied the effects of graded concentrations of ACh (10(-10) to 10(-4) M) in the recirculating perfusate on pulmonary arterial pressure (PAP). The lungs were ventilated to 15 cm of water with 97% O2-3% CO2. ACh (10(-8) to 4 X 10(-7) M) produced a dose-dependent increase in PAP which required up to 20 min to return to predrug levels. Physostigmine (10(-5) M) maintained the maximal PAP response to ACh for the duration of the experiment (up to 2 hr). Higher concentrations of ACh produced rapid increases in PAP resulting in edema. Pre- or post-treatment with the muscarinic receptor antagonist atropine (10(-5) M) completely prevented or reversed the pressor effects of ACh, respectively. Histamine receptor (H1 and H2) or angiotensin II receptor blockade had no effect on the PAP actions of ACh, however pretreatment with the prostaglandin synthesis (cyclooxygenase) inhibitor indomethacin (10(-5) M) or aspirin (10(-3) M), completely abolished the PAP response to ACh up to concentrations of 10(-4) M. In experiments in which airway pressure was allowed to vary, it rose significantly in response to increasing concentrations of ACh. ACh-induced increases in airway pressure were unaffected by pretreatment with indomethacin (10(-5) M) but were totally inhibited by pretreatment with atropine (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects
D011453:Prostaglandins; D001285:Atropine; D000109:Acetylcholine; D001241:Aspirin; D007213:Indomethacin