Influence of nitrovasodilators and endothelin‐1 on rheology of human blood in vitro

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. 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. 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.British Journal of Pharmacology (1999) 128 , 744–750; doi: 10.1038/sj.bjp.0702817