Nagura J, Murayama B, Harada N, Suzuki K, Miyano T, Yajima M, Takeya K
Jpn J Pharmacol. 1986 Mar;40(3):399-409. doi: 10.1254/jjp.40.399.
The cardiovascular effect of NPK-1886 (NPK), a novel photostable dihydropyridine compound, was studied by comparing it with that of nifedipine (Nif). In normal Wistar rats (NWR), systolic blood pressure was only slightly depressed by NPK or Nif, while in three types of hypertensive rats (i.e., spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR) and DOCA-saline-induced hypertensive rats (DOC-Na-R)), the hypotensive potency of NPK was more than or equal to that of Nif. The effectiveness of NPK on the normal and hypertensive models was in the following order: DOC-Na-R, RHR, SHR, NWR. Coronary perfusion flow in Langendorff's heart was increased almost the same extent by NPK and Nif. On isolated rabbit aortic strips, the antagonistic potencies of NPK, like those of Nif, were greater for calcium than for norepinephrine, serotonin and angiotensin II. The negative ino- and chronotropic potency of NPK in isolated guinea-pig right atria was less than that of Nif. The slow membrane action potentials of guinea-pig papillary muscle were suppressed by NPK, but less than by Nif, with manifestations of a reduction of Vmax and AP-duration. These results indicate that NPK has a potent hypotensive effect on hypertensive models and a weaker cardiac inhibition. The general toxicity of NPK was lower than that of Nif.
通过将新型光稳定二氢吡啶化合物NPK - 1886（NPK）与硝苯地平（Nif）进行比较，研究了其心血管效应。在正常Wistar大鼠（NWR）中，NPK或Nif仅使收缩压略有降低，而在三种高血压大鼠（即自发性高血压大鼠（SHR）、肾性高血压大鼠（RHR）和DOCA - 盐水诱导的高血压大鼠（DOC - Na - R））中，NPK的降压效力大于或等于Nif。NPK对正常和高血压模型的有效性顺序如下：DOC - Na - R、RHR、SHR、NWR。NPK和Nif使Langendorff心脏的冠状动脉灌注流量增加的程度几乎相同。在离体兔主动脉条上，NPK的拮抗效力与Nif一样，对钙的作用大于对去甲肾上腺素、5 - 羟色胺和血管紧张素II的作用。NPK对离体豚鼠右心房的负性变力和变时效力小于Nif。豚鼠乳头肌的慢膜动作电位受到NPK的抑制，但程度小于Nif，表现为Vmax和动作电位时程降低。这些结果表明，NPK对高血压模型有强效降压作用，对心脏的抑制作用较弱。NPK的一般毒性低于Nif。
