Cardiotonic agents affect pulmonary vessels in precision-cut lung slices (PCLS)

Introduction: Cardiotonic agents play a major role in the therapy of heart failure. Apart from their effects on ventricular contractility and systemic afterload, they may affect the tone of pulmonary arteries (PAs) and pulmonary veins (PVs). However, in particular the responses of PVs to cardiotonic agents are only poorly defined. Aims and objectives: We investigated the effects of α- and β-adrenergic agents as well as vasopressin in PAs and PVs to clarify their potential role in pulmonary hypertension (PH) or lung edema and coexisting heart failure. Methods: After terminal anaesthesia with pentobarbital, PCLS were prepared from female Dunken Hartley guinea pigs and investigated by video microscopy. Concentration-response curves of various cardiotonic drugs were analyzed in PAs and PVs. Results: After stimulation with α1-adrenergic agents, PAs contracted up to 80.5% ± 3, in respect to the initial vessel area, whereas β2-adrenergic agents showed only little effect. In contrast, after stimulation of α1-receptors PVs contracted up to 77% ± 2.6 and relaxed due to activation of β2-receptors up to 124.7% ± 2.8. Notably, inhibition of β2-receptors unmasked the α1-mimetic effect of (nor)epinephrine. Vasopressin contracted PVs up to 76.4% ± 7.4, without any effect on PAs. Conclusion: Thus, vasoconstriction of PVs enhances capillary and venous hydrostatic pressures and promotes the development of lung edema. Our findings suggest that (nor)epinephrine in combination with unselective β-blockers and vasopressin might be harmful in patients with left heart failure. Further, α1-mimetic agents might exacerbate a pre-existing PH and a failing right ventricle by contracting PAs, whereas vasopressin might not.