Pharmacological characteristics of NP-252, a new dihydropyridine slow Ca2+ channel blocker, in isolated rabbit vascular smooth muscle and guinea pig myocardium: vascular selectivity.
NP-252, a new dihydropyridine derivative, and nifedipine non-competitively inhibited contractile responses to KCl and responses to Ca2+ in Ca(2+)-free medium containing KCl in rabbit aorta and renal, mesenteric, coronary and basilar arteries, mesenteric veins and vena cava. The effects of NP-252 in these smaller arteries and veins were much greater than those in aorta. However, a similar differential selectivity was not seen with nifedipine. In aorta, only NP-252 reduced total La3+ resistant 45Ca binding. However, the increases in bound 45Ca at La3+ resistant sites and 45Ca unidirectional influx due to KCl were inhibited by both NP-252 and nifedipine. The displacement of [3H]nitrendipine binding to rabbit aorta was monophasic for both NP-252 and nifedipine. In guinea-pig papillary muscles, NP-252 (greater than 10(-7) M) slightly decreased action potential duration, developed tension and slow action potentials. The cardiac effects of NP-252 were much less prominent than those of nifedipine. These results indicate that NP-252 inhibits voltage-operated Ca2+ channels in small arteries and veins much more effectively than those in aorta, and this tissue selectivity is more apparent for NP-252 than nifedipine.
Shibata
S
S
University of Hawaii, School of Medicine, Department of Pharmacology, Honolulu 96822.
Satake
N
N
Kodama
I
I
Hester
R K
RK
Wang
C G
CG
Jino
H
H
Hojo
M
M
Tatsumi
H
H
Gandhi
V
V
Jones
D J
DJ
D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D000804:Angiotensin II; C067290:NP 252; D012701:Serotonin; D007811:Lanthanum; D006632:Histamine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine