Differential vasodilator properties of KRN2391, cromakalim, nitroglycerin and nifedipine in rabbit isolated femoral artery and vein.
1. The selectivity for artery and vein of KRN2391, cromakalim, nitroglycerin and nifedipine was examined in isolated femoral artery and vein preparations of the rabbit. 2. All drugs produced a concentration-dependent relaxation in both femoral artery and vein. 3. Nitroglycerin was more potent in femoral vein than in femoral artery at all concentrations. The EC50 value obtained in the vein was about 14 times smaller than that obtained in artery. 4. Cromakalim and nifedipine were almost equipotent on both vascular preparations. Cromakalim at the highest concentration (10(-5) M) produced 88 and 78% relaxation in femoral artery and vein, respectively. The maximum relaxation induced by nifedipine (10(-6) M) was less than 50% in both preparations. 5. KRN2391 was active at a lower concentration in the vein than in the artery and its maximum relaxation at 10(-5) M was about 90% in both preparations. 6. Glibenclamide (10(-6) M) inhibited the vasorelaxation caused by KRN2391 in both artery and vein. Methylene blue (10(-5) M) also inhibited the relaxant action of KRN2391 but this action was slight in the artery. 7. These results suggest that KRN2391 and nitroglycerin are more potent in the vein than in the artery and cromakalim and nifedipine are equipotent in both. It is considered that the relaxation induced by low concentrations of KRN2391 reflects predominantly its action as a nitrate and that at high concentrations it acts as a K+ channel opener in addition to its nitrate action. The different vascular selectivities of these drugs are thought to relate to the differences in their mechanisms of action in vascular smooth muscle.
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd. Gunma, Japan.
T
T
Kashiwabara
N
N
Ogawa
T
T
Izawa
H
H
Fukushima
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D005268:Femoral Vein / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D011725:Pyridines; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D005996:Nitroglycerin; D009543:Nifedipine