Cardiovascular effects of NPK-1886, a new dihydropyridine compound with calcium entry blocking activity.
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.
J
J
Nagura
B
B
Murayama
N
N
Harada
K
K
Suzuki
T
T
Miyano
M
M
Yajima
K
K
Takeya
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000633:toxicity; D002319:Cardiovascular System / Q000187:drug effects*; D004095:Dihydropyridines; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C048962:NPK 1886; D009543:Nifedipine