KRN2391、硝酸甘油和克罗卡林对二氢麦角胺处理的去大脑大鼠的心血管作用。

Cardiovascular effects of KRN2391, nitroglycerin and cromakalim in dihydroergotamine-treated pithed rats.

Kaneta S, Kashiwabara T, Tanaka Y, Yokoyama T, Izumi H, Izawa T, Ogawa N

Pharmaceutical Research Laboratory, KIRIN Brewery Co., Ltd., Gunma, Japan.

Gen Pharmacol. 1994 Sep;25(5):963-8. doi: 10.1016/0306-3623(94)90104-x.

Abstract

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.

摘要

为了研究这些药物对静脉血管的作用，在给予二氢麦角胺（DHE）的脊髓损伤大鼠中，比较了KRN2391与硝酸甘油和克罗卡林对心血管系统的影响。2. DHE（100微克/千克，静脉注射）基于静脉收缩使平均血压（MBP）、心输出量（CO）和中心静脉压（CVP）升高，而总外周血管阻力（TPR）和心率（HR）无变化。在经DHE处理的脊髓损伤大鼠中，硝酸甘油（30微克/千克，静脉注射）使CO和CVP降低，而克罗卡林（30微克/千克，静脉注射）使CO略有升高，随后降低，且不影响CVP。KRN2391（30微克/千克，静脉注射）使CVP降低，而不影响CO。所有药物均引起MBP和TPR降低。3. 这些结果表明，在经DHE处理的脊髓损伤大鼠中，硝酸甘油主要起静脉扩张剂的作用，KRN2391和克罗卡林除具有动脉扩张作用外，还表现出静脉扩张作用。然而，在此条件下KRN2391的静脉扩张作用比克罗卡林更强。