Role of endothelium, oxygen and ionic milieu in the prostacyclin and thromboxane production of rat aortic tissue slices.
The present study was executed in order to get further data on the role of vessel wall constituents in prostanoid synthesis and on the effect of anorganic constituents on it. Prostacyclin and tromboxane production of rat aortic tissue slices with intact endothelium and after mechanical as well as chemical endothelium removal were studied. The effects of hypoxia and changes in the ionic milieu on the release of these prostanoids were also examined. The tissue slices were incubated in normal or in modified Krebs-Ringer solution, bubbled with 95% O2 and 5% CO2 (with the exception of the studies in hypoxic conditions). Prostacyclin and thromboxane release was determined by specific radioimmunoassay of the stable metabolites, 6-keto-PGF1 alpha and TxB2, from the incubation medium. 174 tissue samples obtained from 164 rats were studied. Mechanical removal of the endothelium increased prostacyclin production of the aortic segments about fivefolds from a basal rate of 52.9 +/- 19.4 ng/gr/min, while it had no significant effect on thromboxane release (basal rate 0.83 +/- 0.13 ng/gr/min). Treating the endothelium with 1.0 M HCl almost totally suppressed prostacyclin release. Lowering the partial oxygen tension of the incubation medium significantly decreased the production of prostacyclin, while release of TxB2 somewhat increased. Increasing the Ca2+ concentration of the medium between 0-5 mM the release of prostacyclin was augmented and the release of thromboxane was diminished. Potassium free medium caused a very large increase in prostacyclin release of the tissue slices. The results show that release of vasoactive prostanoids from isolated rat aortic wall is dependent not exclusively on the endothelium and that various methods of endothelium removal may have distinct influences on prostacyclin and thromboxane productions. The changes in anorganic constituents of the surrounding medium could massively affect prostacyclin and thromboxane production of rat aortic tissue. The alternative effects of the above listed treatments on the release of prostacyclin and thromboxane from the rat aortic wall suggest the existence of different mechanisms in the control of the production of the two major prostanoids possessing opposite physiological effects.
Nádasy
G L
GL
Experimental Research Department, Semmelweis Medical University, Budapest, Hungary.
Székács
B
B
Juhász
I
I
Fehér
J
J
Kovách
A G
AG
Monos
E
E
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000494:pharmacology; D013931:Thromboxanes / Q000096:biosynthesis*
D011453:Prostaglandins; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D010100:Oxygen; D002118:Calcium