title: Mepindolol protection of prostacyclin formation. Subsequent increase in arachidonic acid-induced prostacyclin release in isolated guinea pig heart.
abstract: The infusion of arachidonic acid through Langendorff-perfused guinea pig hearts in vitro for 15 min was associated with an increased PGI2 formation and release. This was a transient reaction, which showed a peak after 3-5 min and declined thereafter. Simultaneous infusion of washed human platelets (4 X 10(8)/min) stimulated the peak PGI2 formation (measured as immunoreactive 6-oxo-PGF1 alpha) but did not antagonize the inactivation of the PGI2-forming mechanism(s) in the vessel wall. The beta-adrenoceptor-blocking agent mepindolol (0.3 and 3 microgram/ml) significantly enhanced the peak release of PGI2 at 3 microgram/ml (P less than 0.05). Its major effect, however, was to inhibit the decline in PGI2 release during arachidonic acid infusion. In this case the PGI2 release during arachidonic acid infusion (area under the curve) was doubled in the presence of mepindolol at both concentrations. It is concluded that protection of vascular PGI2 formation from inactivation might be an important mechanism for the maintenance of PGI2 release in response to continuous stimuli.
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001792:Blood Platelets / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis* / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*
chemical_list: D001095:Arachidonic Acids; D011453:Prostaglandins; C015340:mepindolol; D016718:Arachidonic Acid; D010869:Pindolol; D011464:Epoprostenol