Tsuda Y, Satoh K, Kitadai M, Izumi Y, Takahashi T
Second Department of Internal Medicine, Kagawa Medical School, Japan.
Arzneimittelforschung. 1997 Aug;47(8):900-4.
Because blood viscosity is significantly raised in patients with essential hypertension (EH), the hemorheological effects of a 4-month chronic treatment with the calcium antagonist nilvadipine (FK 235, 5-isopropyl-3-methyl-2-cyano-1,4-dihydro-6-methyl-4- (m-nitrophenyl)-3,5-pyridinedicarboxylate, CAS 75530-68-6) on elevated blood viscosity was investigated prospectively in patients with EH, and compared with those in normotensive individuals of similar age. Hemorheological parameters were measured in 13 patients with EH (mean 63.7 years), before and 16.3 weeks (mean) after treatment with 8 mg nilvadipine, twice a day, following a 2-week placebo period, and in 14 normotensive individuals (mean 65.8 years). Whole blood viscosity of 45.0-562.5 s-1 shear rates and corrected blood viscosity of low (45.0 s-1) and high (225.0 s-1) shear rates at standardised hematocrit (Ht) of 45%, plasma viscosity, Ht, serum albumin, and plasma fibrinogen were measured before and after drug treatment and compared with those in normotensive individuals. Whole-blood and plasma viscosities were measured by cone-plate viscometer. Systolic and mean blood pressures (BPs), whole blood viscosities (at low and middle shear rates), corrected blood viscosity (Ht 45% at a low shear rate), and plasma viscosity were higher in patients with EH than in normotensive individuals before medication (p < 0.001 to p < 0.01). All these parameters decreased significantly after nilvadipine (p < 0.004 to p < 0.05). On the other hand, serum albumin and plasma fibrinogen were not altered significantly after nilvadipine. Ht decreased but not significantly after nilvadipine. Mean BP correlated with corrected blood viscosities at 112.5 s-1 and 225.0 s-1 (r = 0.491 p < 0.01 and r = 0.537 p < 0.005), while systolic BP did not correlate, before and after nilvadipine. Chronic treatment with calcium antagonist nilvadipine brought about significant reductions in BPs and rheological parameters of whole-blood viscosities at low and middle shear rates, corrected blood viscosity (Ht 45%) at a low shear rate, and plasma viscosity without changes in serum albumin and plasma fibrinogen levels, as compared with normotensive individuals. Significant linear correlations between values of mean BP and corrected blood viscosities before and after milvadipine show improved hemorheology in association with BP reduction in EH. Vasodilative effects of nilvadipine may have improved the blood rheology in patients with EH.
由于原发性高血压(EH)患者的血液粘度显著升高,因此前瞻性地研究了钙拮抗剂尼伐地平(FK 235,5-异丙基-3-甲基-2-氰基-1,4-二氢-6-甲基-4-(间硝基苯基)-3,5-吡啶二甲酸酯,CAS 75530-68-6)对EH患者血液粘度升高的血液流变学影响,并与年龄相仿的血压正常个体进行比较。在13例EH患者(平均63.7岁)中,在为期2周的安慰剂期后,每天两次服用8 mg尼伐地平治疗前及治疗后16.3周(平均)测量血液流变学参数,并在14例血压正常个体(平均65.8岁)中进行测量。在标准化血细胞比容(Ht)为45%的情况下,测量45.0 - 562.5 s-1剪切率下的全血粘度以及低(45.0 s-1)和高(225.0 s-1)剪切率下的校正血液粘度、血浆粘度、Ht、血清白蛋白和血浆纤维蛋白原,在药物治疗前后进行测量,并与血压正常个体进行比较。全血和血浆粘度通过锥板粘度计测量。EH患者用药前的收缩压和平均血压(BP)、全血粘度(低和中剪切率)、校正血液粘度(低剪切率下Ht 45%)和血浆粘度均高于血压正常个体(p < 0.001至p < 0.01)。尼伐地平治疗后所有这些参数均显著降低(p < 0.004至p < 0.05)。另一方面,尼伐地平治疗后血清白蛋白和血浆纤维蛋白原无明显变化。尼伐地平治疗后Ht有所下降,但不显著。平均BP与112.5 s-1和225.0 s-1下的校正血液粘度相关(r = 0.491,p < 0.01;r = 0.537,p < 0.005),而尼伐地平治疗前后收缩压无相关性。与血压正常个体相比,钙拮抗剂尼伐地平的长期治疗使BP以及低和中剪切率下的全血粘度、低剪切率下的校正血液粘度(Ht 45%)和血浆粘度等流变学参数显著降低,而血清白蛋白和血浆纤维蛋白原水平无变化。平均BP值与尼伐地平治疗前后校正血液粘度之间存在显著的线性相关性,表明EH患者血液流变学改善与血压降低相关。尼伐地平的血管舒张作用可能改善了EH患者的血液流变学。