Release of prostacyclin from the human pulmonary vascular bed in response to cholinergic stimulation

Abstract

The ability of the human pulmonary vascular bed to synthesize prostaglandins (PGs) in response to cholinergic stimulation was investigated in healthy male volunteers. In all of them, except controls, carbaminoylcholine (CCh) was injected subcutaneously at a dose of 5 micrograms/kg. In 3 subjects [1-14C]-labelled arachidonate was then infused at a constant rate into the right atrium between 10 and 15 min after the administration of the drug and the blood from the subclavian artery was sampled simultaneously. The arterial content of [14C]-labelled metabolites was extracted, separated by thin-layer chromatography and quantified using liquid scintillation spectrometry. In 8 other subjects PGI2-like activity after the administration of CCh was assayed in the arterial blood and in 1 subject in the venous blood, using a technique for continuous measurement of platelet aggregation on blood-superfused collagen strip. The major portion of [14C]-activity in the radiochromatograms migrated in parallel with the 6-keto-PGF1 alpha standard. No early defined peaks corresponding to any of the unlabelled PGs D2, E2 or F2 alpha, appeared, but in one chromatogram a minor radiopeak corresponding to authentic thromboxane B2 was observed. Also in the platelet aggregation experiments, 5-15 min after the administration of CCh, a significant increase in the PGI2-like activity was observed in the arterial as well as in the peripheral venous blood, which effect of the drug was abolished by pretreatment with atropine and acetylsalicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging-Shifted Prostaglandin Profile in Endothelium as a Factor in Cardiovascular Disorders

“…In endothelium, the expression levels of the PGESs are comparable to other PG synthases [54, 64, 65, 84]. Consistently, the amount of PGE 2 in endothelium is comparable to other PGs, but lower than the amount of PGI 2 [54, 97, 107–110, 125]. In further accord, the contribution of PGE 2 to endothelium-dependent vasoaction is marginal [84, 125].…”

“…In endothelium, PGIS is by far the most abundant PG terminal synthase, with its expression level 5–100-fold higher than the other PG terminal synthases [ 54 , 64 , 65 , 84 ]. Accordingly, PGI 2 is the most abundant endothelial eicosanoid, with expression levels 10–100-fold higher than that of the other eicosanoids in humans [ 107 , 108 ] and in animals [ 54 , 97 , 109 , 110 ].…”

“…They are transformed from PGH 2 by the membrane-associated 9,11-endoperoxide reductase and from PGD 2 /PGE 2 by cytosolic PGD 2 11-ketoreductase/PGE 2 9-ketoreductase, respectively [ 138 , Figure 1]. In endothelium, the level of PGF 2 α is similar to that of PGE 2 , but much lower than that of PGI 2 [ 54 , 97 , 107 – 110 , 125 ], corresponding to low abundance of PGF 2 α cognate synthase (PGFS) in the endothelium [ 54 , 64 , 65 , 84 ].…”

Prostanoid Receptors in the Human Vascular Wall

“…These responses were partially inhibited by a nonselective COX inhibitor (indomethacin) and they are dependent on PGI 2 release by the endothelium. In these vascular cells or tissue, the production of PGI 2 was two-to eightfold greater in comparison with the other prostanoids synthesized [22,23]. These measurements are dependent on the initial COX-1 activity and not the COX-2 activity, since immunohistochemistry experiments and/or western-blot analysis have shown a preferential presence of the COX-1 in the endothelium of ovarian, pulmonary, or aortic vessels [24,25,26,27].…”

Mediators produced by the endothelial cell.

“…Bradykinin and choline esters may have the strongest case, for they are potent and release prostacyclin from endothelial cells into the culture medium 21 -62 and from tissues into the blood stream of humans 63 and animals. 18 Other vasoactive peptides, such as angiotensin I and angiotensin II, which release prostacyclin from perfused lungs 71 and blood vessels of anesthetized cats, 18 are not good candidates as endogenous regulators of the release of prostacyclin.…”