EFFECTS OF ENDOTHELIN ON HEMODYNAMICS, PROSTAGLANDINS, BLOOD-COAGULATION AND RENAL-FUNCTION

The interaction of the endogenous vasoconstrictors endothelin (ET), angiotensin II (Ang II) and catecholamines with the kallikrein-kinin-, prostaglandin and renin-aldosterone systems in the pathogenesis of acute renal failure (ARF) is still to be defined. In 18 anesthesized pigs the influence of i.v. bolus applications of ET (2 mu g/kg), Ang II (10 mu g/kg) and norepinephrine (NE; 20 mu g/kg) on hemodynamics, plasmatic coagulation and fibrinolysis system, prostaglandins and renal function was studied. ET induced a biphasic change in blood pressure, starting with an initial short-lasting reduction followed by a long-lasting elevation of systolic and diastolic blood pressure. Endothelin bolus resulted in a significant increase of 6-keto-PGF(1) alpha, PGE(2) and TXB(2) plasma levels (P < 0.05 against preinjection values), whereas prostaglandins remained unchanged in the Ang II and NE groups. There was a distinct correlation between the plasma ET and 6-keto-PGF(1) alpha levels (r = 0.82). In contrast to Ang II or NE, ET induced a shortening of the activated partial thromboplastin time (aPTT) and increase of antithrombin III levels (ATIII), fibrin monomers (FM), prekallikrein (PKK) and factor VIII activity at the beginning. Finally a pronounced decrease of ATIII, FM and PKK occurred, indicating a consumptive coagulopathy. At the end of the experiment, elevated plasma renin activity and pCO(2), significantly decreased creatinine clearance, blood pH, pO(2), base excess, HCO3-, oxygen saturation (P < 0.01), a distinct glomerular proteinuria, and a final anuria were observated. These results reveal that ET activates the plasmatic coagulation system and induces an ARF accompanied by impairment of pulmonary function. Its coagulation activating and renal vasoconstrictive effects may be important pathophysiological factors, especially when the counteractive release of vasodilatatory and antiaggregatory prostacyclin or NO is impaired.