Effects of endothelin on hemodynamics, prostaglandins, blood coagulation and renal function

Abstract

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)

Structure and Function of Smooth Muscle with Special Reference to Mast Cells

“…Apart being a potent vasoconstrictor, ET-1 also exhibits hypertrophic, mitogenic and anti-apoptotic effects on vascular smooth muscle cells [50][51][52]. EТ-1 induces strong and prolonged contractile responses in vascular smooth muscle cells in different systems, with a special effect on the renal vascular bed [48,[53][54][55][56]. Initially described as a vasoconstrictor, ET-1 is now acknowledged to participate in the pathogenesis of a number of disorders, i.e.…”

Endothelin, angiotensin II and adenosine in acute cyclosporine A nephrotoxicity

“…Moreover, it was shown that the i.v. administration of ET causes a dose-dependent alteration in renal function that has close similarities to that of CsA administration (i.e., increased RVR with subsequent decreased RBF and GFR), suggesting that ET could mediate this phenomenon [6,7,8,9].…”

“…administration of ET was shown to cause a dose-dependent and long-lasting decrease in RBF, GFR and urine volume as a result of increased RVR, mesangial cell contraction and decreases in the ultrafiltration coefficient [6,7,8,9]. The decrease in RBF involves vascular contraction of both cortex and medulla with vasoconstriction involving preand postglomerular arterioles as well as the arcuate and interlobular arteries [8].…”

Effect of Endothelin Receptor Antagonist (TAK-044) on Autotransplanted Perfused Kidneys in Dogs

“…In a study of acute renal failure in pigs, the administration of ET-1 suggested that ET-1 caused renal dysfunction by severely reducing renal blood flow and the glomerular filtration rate [14]. In patients with chronic renal failure, including those undergoing hemodialysis or continuous ambulatory peritoneal dialysis, ET-1 is elevated in comparison with normal volunteers [15].…”