Endocardial endothelium modulates cardiac responses to histamine and impromidine in isolated working right ventricle of guinea pigs.

In isolated working right ventricle of guinea pigs, the hypothesis that endocardial endothelium (EE) might be involved in the modulation of cardiac responses to histamine receptor agonists was tested. The functional EE was denuded by switching Krebs perfusion solution to the solution containing saponin (30 micrograms.ml-1) for 2 min at a rate of 16 ml.min-1, followed by thorough washing with Krebs solution. The cardiac responses to histamine receptor agonists were compared in the presence and absence of EE. Bolus injection of histamine 0.5 mg into right ventricle elevated the right ventricular pressure (RVP), +dP/dtmax, and -dP/dtmax by 11%, 17%, and 35%, respectively, in the presence of intact EE; whereas by 30%, 43%, and 92%, respectively, after chemically selective denudation of EE with saponin. Similarly, impromidine (a H2 receptor agonist) 1, 3, 9, 27, and 54 micrograms obviously potentiated the RVP and +/- dP/dtmax in a concentration-dependent manner in preparations either with or without EE. The effects, however, could be greatly enhanced in the absence of EE. Pulmonary outflow was declined at 27 micrograms impromidine in EE-removed group. The results suggested that the augmentation of cardiac responses produced by histamine receptor agonists in EE-denuded preparations might be due to blockade of release of endothelium-derived relaxing factor, resulting in a reduced abbreviating effect on the myocardial contraction.