The effect of portal hypertension (induced by partial ligation) on the ability of the portal vein wall to produce prostacyclin (PG12) was studied in rats over a period of 6 weeks. PG12-like activity measured by bioassay was shown to be significantly increased in portal vein segments during established hypertension when compared to control groups. As a collateral circulation developed with consequent fall in portal venous pressure, PGIz -like activity decreased. A positive correlation between PGL-like activity and portal pressure has been demonstrated. Parallel measurements of this activity by bioassay and radioimmunoassay to 6-keto-prostaglandin-F1 a showed a positive correlation (r = 0.88) and suggested that PGIz is the inhibitory prostaglandin involved. The possible significance of these observations in relation to the hemorrhagic manifestations associated with portal hypertension in man is discussed.
Prostacyclin (PG12) is a potent vasodilator and inhibitor of platelet aggregation. It is produced by vascular endothelium of many species including the rat and man (1,2). As well as being an important mediator of plateletvessel wall interaction, it may be a circulating hormone, one of the functions of which is to counteract the proaggregatory property of thromboxane, a prostaglandin derivative generated endogenously in stimulated platelets (3) (Figure 1).
The demonstration of alteration in PGI:! stimulating or inhibiting activity of plasma from patients with a number of diseases associated with hemorrhage or thrombotic complications suggests the possibility that PGIz has some clinical relevance (4). Van Hoof et al. have reported groups of patients with liver or renal disease having raised levels of PGIz stimulating factors in their plasma (5). Pace-Asciak et al. found increased PGIz activity in aortas of spontaneously hypertensive rats, and suggested that this might be an adaptive response to hypertension (6). We have demonstrated significantly greater PGI:! activity in rat portal vein wall 1 week after partial ligation of the vein sufficient to induce hypertension (7).
These observations led us to postulate that increased production of PGIz by portal vein wall in response to ~