Opposing actions of cholinergic agonist and trinitroglycerin on net vascular resistance in perfused rat heart

The effects of cholinergic agonist and nitrovasodilator on transorgan pressure-flow relationships were characterized under antegrade aortic perfusion of the rat heart. Under basal conditions, the preparation exhibited a stable linear dependence of perfusion pressure upon regulated transorgan flow rate from 0 to 9 ml/min with a transorgan vascular resistance of 5 +/- 0.6 mmHg/ml per min. Maximal acetyl-beta-methacholine (10 microM) caused a 3-fold increase in net transorgan vascular resistance to flow of non-cellular perfusate as observed over the range of constant flow rates from 1 to 8 ml/min. Trinitroglycerin (20 microM) reversed cholinergic-induced vasoconstriction. The effects of acetylcholine on transorgan flow were characterized at constant perfusion pressures approximating mean aortic pressures under lethal hypotension (40 mmHg), sublethal hypotension (70 mmHg) and normotension (100 mmHg). Under maximal acetylcholine (5 microM), flow remained adequate at 4.6 ml/min under 100 mmHg aortic pressure, marginally adequate at 1.2 ml/min under 70 mmHg, and sublethally inadequate at 0.4 ml/min under 40 mmHg. It is concluded that acetylcholine is among the factors increasing vascular resistance that can be opposed by nitrovasodilator. It is estimated that inadequate flow might result from maximal cholinergic agonist under hypotensive but apparently not normotensive aortic perfusion pressure as observed in hearts from normal animals.