Endothelin-1 potentiates ADP-induced platelet aggregation in chronic renal failure.
The effect of preincubation of heparinized whole blood with endothelin-1 (ET-1) on the ADP (adenosine diphosphate) and epinephrine-induced platelet aggregation was examined in 20 healthy donors compared with 20 patients with chronic renal failure (CRF). ET-1 significantly stimulated ADP-induced aggregation in CRF: EC (effective concentration)25 = 2.3 +/- 0.20 with ET-1 vs. 2.7 +/- 0.22 mumol/L without ET-1; EC50: 3.8 +/- 0.18 with ET-1 vs. 4.4 +/- 0.24 mumol/L without ET-1; and EC75: 5.7 +/- 0.22 with ET-1 vs. 6.4 +/- 0.21 mumol/L without ET-1). In healthy donors only the EC25 was significantly increased: EC25 = 2.5 +/- 0.13 with ET-1 vs. 2.8 +/- 0.20 mumol/L without ET-1. No significant influence of ET-1 in epinephrine-induced aggregation was observed in CRF or in healthy donors. The basal values of determined ET-1 were significantly elevated in CRF: 6.99 +/- 0.29 pmol/mL vs. 5.65 +/- 0.33 pmol/mL in healthy donors. The high endogenous level of ET-1 in CRF patients together with an observed higher endogenous plasma level of cAMP (58 +/- 5.2 nmol/L compared to 29 +/- 2.0 nmol/L in healthy donors) may explain the enhanced pharmacological interaction of ET-1 and ADP in CRF patients. The data suggest that positive agonist interaction between ET-1 and ADP may result from effects on the concentrations of cAMP within the platelet rather than from direct interaction on the membrane receptors or the transmembrane coupling mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Heintz
B
B
Medical Clinic II, Technical University of Aachen, Germany.
Schmidt
P
P
Maurin
N
N
Kirsten
R
R
Nelson
K
K
Wieland
D
D
Sieberth
H G
HG
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D001782:Blood Donors; D000242:Cyclic AMP / Q000097:blood; D016232:Endothelins / Q000494:pharmacology* / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*
D016232:Endothelins; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D004837:Epinephrine