Cardiovascular agents affect the tone of pulmonary arteries and veins in precision-cut lung slices.
BACKGROUND
Cardiovascular agents are pivotal in the therapy of heart failure. Apart from their action on ventricular contractility and systemic afterload, they affect pulmonary arteries and veins. Although these effects are crucial in heart failure with coexisting pulmonary hypertension or lung oedema, they are poorly defined, especially in pulmonary veins. Therefore, we investigated the pulmonary vascular effects of adrenoceptor agonists, vasopressin and angiotensin II in the model of precision-cut lung slices that allows simultaneous studies of pulmonary arteries and veins.


METHODS
Precision-cut lung slices were prepared from guinea pigs and imaged by videomicroscopy. Concentration-response curves of cardiovascular drugs were analysed in pulmonary arteries and veins.


RESULTS
Pulmonary veins responded stronger than arteries to α(1)-agonists (contraction) and β(2)-agonists (relaxation). Notably, inhibition of β(2)-adrenoceptors unmasked the α(1)-mimetic effect of norepinephrine and epinephrine in pulmonary veins. Vasopressin and angiotensin II contracted pulmonary veins via V(1a) and AT(1) receptors, respectively, without affecting pulmonary arteries.


CONCLUSIONS
Vasopressin and (nor)epinephrine in combination with β(2)-inhibition caused pulmonary venoconstriction. If applicable in humans, these treatments would enhance capillary hydrostatic pressures and lung oedema, suggesting their cautious use in left heart failure. Vice versa, the prevention of pulmonary venoconstriction by AT(1) receptor antagonists might contribute to their beneficial effects seen in left heart failure. Further, α(1)-mimetic agents might exacerbate pulmonary hypertension and right ventricular failure by contracting pulmonary arteries, whereas vasopressin might not.
Department of Anaesthesiology, Institute of Pharmacology and Toxicology, Medical Faculty Aachen, RWTH-Aachen, Aachen, Germany. arieg@ukaachen.de
Annette D
AD
Rieg
Rolf
R
Rossaint
Stefan
S
Uhlig
Christian
C
Martin
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply*; D009129:Muscle Tonus / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011667:Pulmonary Veins / Q000187:drug effects* / Q000502:physiology
D002317:Cardiovascular Agents