Comparative influence of the Ca-ionophore A 23187, bradykinin, kallidin and eledoisin on the rabbit pulmonary vasculature with special reference to arachidonate metabolism.
In a model of isolated rabbit lungs, perfused with isoionic and isooncotic fluid in a recirculating system, the Ca-ionophore A 23187, bradykinin, (kallidin), and eledoisin all evoke a reversible and reproducible increase in pulmonary vascular resistance, partly with biphasic characteristics. Inhibition of thromboxane-synthetase (imidazole), cyclooxygenase (indomethacin) phospholipase activity (mepacrine), and interference with the Ca-calmodulin-complex (trifluoperazine) each suppresses the increase in resistance due to A 23187 or eledoisin completely and the increase due to bradykinin or kallidin to a great extent. Thus thromboxane A2 appears to be the mainly responsible mediator for the increase in vascular resistance after all three stimuli. Moreover, A 23187 and bradykinin cause an increase in vascular permeability that is augmented by indomethacin and diminished by additional lipoxygenase inhibition with BW 352C and which thus can, at least partly, be ascribed to lipoxygenase products of released arachidonic acid. In spite of the described similarities there are marked differences in the relative potencies of A 23187, bradykinin and eledoisin concerning the increase in vascular resistance and the increase in vascular permeability. Therefore, different stimulus transmission-pathways are suggested, having Ca-calmodulin-complex, phospholipase activity and arachidonic acid transformation via cyclooxygenase/thromboxane synthetase respectively via lipoxygenases as common characteristics.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004600:Eledoisin / Q000494:pharmacology*; D007609:Kallidin / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001095:Arachidonic Acids; D007609:Kallidin; D000001:Calcimycin; D004600:Eledoisin; D001920:Bradykinin