Effect of KRN2391 on venous return: comparison with other vasodilators.
We compared the cardiohemodynamic effects of KRN2391, a novel coronary vasodilator, with those of nicorandil, nifedipine, cromakalim, and nitroglycerin (NTG) administered intravenously (i.v.) to anesthetized open-chest dogs. KRN2391 (10 and 30 micrograms/kg) decreased mean blood pressure (MBP) and superior vena cava flow (SVCF), and increased inferior vena cava flow (IVCF), total venous return (TVR), pulmonary artery blood flow (PAF), and right atrial pressure (RAP). Administration of KRN2391 (30 micrograms/kg) decreased heart rate (HR). Nicorandil (100 and 300 micrograms/kg) decreased MBP and SVCF, and produced transient increases followed by decreases in IVCF, TVR, PAF, and RAP. HR was decreased by administration of nicorandil (300 micrograms/kg). Nifedipine (1 and 3 micrograms/kg) decreased MBP and increased SVCF, IVCF, TVR, PAF, and RAP. HR was not affected by either dose of nifedipine. Cromakalim (10 micrograms/kg) decreased MBP, SVCF, and increased HR, IVCF, TVR, PAF and RAP. Nitroglycerin (3 micrograms/kg) decreased MBP, SVCF, IVCF, TVR, PAF, and RAP. In dogs that received glibenclamide (5 mg/kg, i.v.), the changes in MBP, SVCF, IVCF, TVR, PAF, and RAP caused by KRN2391 were reduced in comparison with those in dogs that received vehicle for glibenclamide. The decreases in IVCF, TVR, and PAF induced by nicorandil were not affected by glibenclamide, but the decrease in MBP was diminished and the decrease in RAP was augmented. The hemodynamic changes caused by cromakalim were almost inhibited by glibenclamide, whereas those caused by NTG were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaneta
S
S
Pharmaceutical Research Laboratory, Kirin Brewery, Gunma, Japan.
Jinno
Y
Y
Miwa
A
A
Fukushima
H
H
Ogawa
N
N
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D020108:Nicorandil; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects*
D001578:Benzopyrans; D015221:Potassium Channels; D011725:Pyridines; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D009536:Niacinamide; D020108:Nicorandil; D005996:Nitroglycerin; D009543:Nifedipine; D005905:Glyburide