Comparative effects of the calcium antagonist isradipine and some other dihydropyridine derivatives on regional blood flow in anesthetized open-chest dogs.
The effects of isradipine (PN 200-110), isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-5-methoxycarbonyl-2,6-dim ethyl-3- pyridinecarboxylate, on some cardiovascular parameters and regional blood flow were compared with those of other dihydropyridine derivatives in anesthetized open-chest dogs. Intravenous (i.v.) administrations of isradipine 3 and 10 micrograms/kg, nifedipine 10 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg, decreased aortic blood pressure and increased aortic (AoF), vertebral (VBF) and coronary blood flow (CBF), but did not affect heart rate and left ventricular end-diastolic pressure. Renal blood flow was reduced by isradipine 10 micrograms/kg and nifedipine 10 micrograms/kg, but was not influenced by isradipine 3 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg. Left ventricular dP/dt was increased by isradipine 3 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg, but remained essentially unchanged following isradipine 10 micrograms/kg and nifedipine 10 micrograms/kg. The increase in AoF, VBF and CBF lasted 5-9 min following nifedipine 10 micrograms/kg or nicardipine 10 micrograms/kg, 17-30 min following nifedipine 10 micrograms/kg or nicardipine 10 micrograms/kg, 17-30 min following nisoldipine 10 micrograms/kg, and 16-44 min following isradipine 3 micrograms/kg i.v., but persisted for at least 60 min following isradipine 10 micrograms/kg. Under the experimental conditions and at the doses used in this study, all 4 drugs reduced total peripheral resistance as well as resistance in the vertebral, coronary and renal vascular beds. The results suggest that isradipine exerts cardiovascular effects similar to other calcium antagonists of the dihydropyridine group, but possesses a longer duration of action and shows a greater specificity in reducing coronary vascular resistance than nifedipine, nicardipine and nisoldipine.
Sakanashi
M
M
Department of Pharmacology, School of Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Noguchi
K
K
Miyamoto
Y
Y
Kato
T
T
Nagamine
F
F
Yu
W Y
WY
Higuchi
M
M
Nakasone
J
J
D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D017275:Isradipine; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D011725:Pyridines; D017275:Isradipine