Cardiovascular effects of KRN2391, nitroglycerin and cromakalim in dihydroergotamine-treated pithed rats.
1. The effects of KRN2391 on the cardiovascular system were compared with those of nitroglycerin and cromakalim in pithed rats treated with dihydroergotamine (DHE) in order to examine the effects of these drugs on venous blood vessels. 2. DHE (100 micrograms/kg, i.v.) produced increases in mean blood pressure (MBP), cardiac output (CO) and central venous pressure (CVP) without changes in total peripheral vascular resistance (TPR) and heart rate (HR) based on venoconstriction. The DHE-treated pithed rats, nitroglycerin (30 micrograms/kg, i.v.) decreased CO and CVP whereas cromakalim (30 micrograms/kg, i.v.) produced a slight increase in CO followed by a decrease and did not affect CVP. KRN2391 (30 micrograms/kg, i.v.) produced a decrease in CVP without affecting CO. Decreases in MBP and TPR were induced by all drugs. 3. These results suggest that nitroglycerin acts predominantly as a venodilator and KRN2391 and cromakalim showed a venodilating action in addition to an arterial dilating action in DHE treated pithed rats. However, the venodilating action of KRN2391 in this condition is more potent than that of cromakalim.
Kaneta
S
S
Pharmaceutical Research Laboratory, KIRIN Brewery Co., Ltd., Gunma, Japan.
Kashiwabara
T
T
Tanaka
Y
Y
Yokoyama
T
T
Izumi
H
H
Izawa
T
T
Ogawa
N
N
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D003655:Decerebrate State; D004087:Dihydroergotamine / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; 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; D004087:Dihydroergotamine; D005996:Nitroglycerin