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)
Schulz
E
E
Department of Nephrology/Rheumatology, University of Göttingen, Germany.
Ruschitzka
F
F
Lueders
S
S
Heydenbluth
R
R
Schrader
J
J
Müller
G A
GA
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D001784:Blood Gas Analysis; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000097:blood*; D013552:Swine
D016232:Endothelins; D011453:Prostaglandins; D000804:Angiotensin II; D009638:Norepinephrine