Endothelial secretogogues and deformability of erythrocytes.
Many diseases of the heart and circulatory system have been linked with both dysfunction of vascular endothelium and insufficient deformability of erythrocytes. Using shear stress laser diffractometry we investigated whether deformability of erythrocytes would be regulated endogenously by generation of two endothelial secretogogues: prostacyclin and nitric oxide. Experiments were performed in rats ex vivo and with whole blood or isolated erythrocytes in vitro. Iloprost--a stable analogue of prostacyclin (10 microg/kg i.v.) and SIN-1 (NO-donor) at a dose of 2 mg/kg/min i.v induced a significant improvement of deformability of erythrocytes ex vivo. Improvements of deformability by these two compounds were also evident in vitro when they were applied at a range of concentrations of 1 microM and 3 microM, respectively. Cyclooxygenase (indomethacin 20 mg.kg i.v.) and nitric oxide synthase (L-NAME 10 mg/kg i.v.) inhibitors while worsening deformability ex vivo, they did not affect (3 mM and 10 microM, respectively) rheological functions of erythrocytes in vitro. Aggravating effects of these inhibitors on erythrocyte deformability ex vivo were reversed by prostacyclin and nitric oxide supplemented exogenously. Aspirin at a low (1 mg/kg i.v.) and high dose (50 mg/kg i.v.), contrary to indomethacin and L-NAME, aggravated erythrocyte deformability either ex vivo or in vitro. It is concluded that autocrine function of vascular endothelium plays an important role in regulation of rheology of red blood cells in flowing blood. The mechanism of this phenomenon is unclear but some possible explanations are discussed. In addition, in our experiments aspirin revealed unique erythrocyte damaging properties, possibly independent of inhibition of cyclooxygenase, but related to a direct protein acetylation.
Korbut
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Chair of Pharmacology, Department of Pharmacological Analysis, Medical College, Jagiellonian University, Krakow, Poland. mfkorbut@cyf-kr.edu.pl
Adamek-Guzik
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Madej
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Korbut
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D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism* / Q000494:pharmacology; D004907:Erythrocyte Deformability / Q000187:drug effects / Q000502:physiology*; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D016285:Iloprost; D019331:NG-Nitroarginine Methyl Ester