Comparison of hemodynamic effects of nitric oxide (NO) donors with different NO-releasing properties in rats.
The aim of this study was to compare the hemodynamic effects of three nitric oxide (NO) donors [i.e., (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), (+/-)-N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-6-methyl-5-nitro-3-he ptenyl]-3-pyridinecarboxamide (FR 146801) and isosorbide dinitrate (ISDN)] in rats. In in vitro experiments, FK409 had a higher spontaneous NO-releasing rate in solution and more potent vasorelaxant activity in isolated rat aorta than other drugs. FR146801 and ISDN showed almost the same vasorelaxant activity. In in vivo experiments, FK409 significantly decreased hematocrit at 1.0 mg/kg p.o., whereas FR146801 and ISDN significantly decreased it at 10 mg/kg p.o., suggesting that these NO-donating agents cause significant plasma volume expansion. However, only FK409 showed significant hypotensive effects immediately after oral administration even at 0.32 mg/kg; FR146801 and ISDN did not cause any significant hypotension at 10 mg/kg, suggesting that FK409 induces much more potent arterial vasodilation than other drugs. These findings suggest that NO donors induce significant plasma volume expansion and that the differences in the selectivities between these effects and their hypotensive effects is probably produced by their different NO-releasing activities.
Kita
Y
Y
New Drug Research Laboratories, Kashima Yodogawa-ku, Osaka, Japan.
Hirasawa
Y
Y
Kato
Y
Y
Ohkubo
K
K
Ohno
M
M
Nishino
S
S
Kato
M
M
Fukuyama
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D009574:Nitro Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; C108152:FR 146801; D009573:Nitrites; D009574:Nitro Compounds; D014665:Vasodilator Agents; D009536:Niacinamide; D009569:Nitric Oxide; C061872:FK 409; D000254:Sodium-Potassium-Exchanging ATPase; D007548:Isosorbide Dinitrate