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 micrograms/kg), Ang II (10 micrograms/kg) and norepinephrine (NE; 20 micrograms/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-PGF1 alpha, PGE2 and TXB2 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-PGF1 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 pCO2, significantly decreased creatinine clearance, blood pH, pO2, 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.(ABSTRACT TRUNCATED AT 250 WORDS)