title: Influence of nitrovasodilators and endothelin-1 on rheology of human blood in vitro.
abstract: 1. The shear stress of flowing blood profoundly influences the release of endothelium-dependent vasodilative and constrictive factors. Conversely, the influence of these mediators such as nitric oxide (NO) or endothelin-1 (ET-1) on blood rheology remains elusive. In the present study the influence of nitrovasodilators and ET-1 on red blood cell (RBC) shape and whole blood viscosity were investigated. 2. Incubation of whole blood with sodium-nitroprusside (SNP, 10-5 - 10-2 M), glyceryl trinitrate (GTN, 0.0001 - 0.1 mg mL-1), S-nitroso-N-acetylpenicillamine (SNAP, 10-6 - 10-3 M), and the active metabolite of molsidomine (SIN-1, 10-6 - 10-3 M), but not molsidomine (10-6 - 10-3 M), resulted in significantly increased amounts of methaemoglobin, indicating a relevant interaction with RBCs. Treatment with SNP at 10-2 M induced a marked echinocytosis (morphological index: 2.23+/-0.98 vs -0.17+/-0.10; P<0.001) and increased blood viscosity (haematocrit 45%) at a high shear rate of 94.5 s-1 (6.46+/-0.60 vs 5.07+/-0.35 mPa.s; P<0.01) and a low shear rate of 0.1 s-1 (88.6+/-36.8 vs 42.1+/-11.7 mPa.s; P<0.01). Echinocytosis was probably due to cyanide accumulation. SIN-1 at 10-3 M slightly decreased high shear viscosity (4.88+/-0.28 vs 4. 95+/-0.30 mPa.s; P<0.05). SNAP at 10-3 M slightly increased both high (5.14+/-0.23 vs 5.05+/-0.24 mPa.s; P<0.01) and low shear (53.9+/-7.2 vs 51.2+/-5.9 mPa.s; P<0.05) viscosity. Molsidomine and GTN failed to influence whole blood viscosity. ET-1 (10-9 - 10-6 M) had no effect on RBC shape and viscosity. 3. We conclude that the most important modulators of vascular tone, NO and ET-1, do not affect RBC shape and blood viscosity, which is important from both a physiological and a pharmacological point of view.
authors.affiliation: Internal Medicine, Kantonsspital, CH-7000 Chur, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Walter
authors.forename: M
authors.initials: M
authors.lastname: Mark
authors.forename: R
authors.initials: R
authors.lastname: Gaudenz
authors.forename: L G
authors.initials: LG
authors.lastname: Harris
authors.forename: W H
authors.initials: WH
authors.lastname: Reinhart
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology; D001809:Blood Viscosity / Q000187:drug effects*; D019332:Endothelin-1 / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008854:Microscopy, Electron; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D019332:Endothelin-1; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D006493:Heparin; D005996:Nitroglycerin