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.