Shinde Urmila A, Desai Kaushik M, Yu Changhua, Gopalakrishnan Venkat
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5E5 Canada.
J Hypertens. 2005 Apr;23(4):779-84. doi: 10.1097/01.hjh.0000163146.20330.bc.
To investigate the mechanism underlying the observation that infusion of the growth hormone secretagogue peptide, ghrelin, produces a decrease in mean arterial pressure (MAP) with no change in heart rate.
The effect of a single bolus infusion of ghrelin (12 nmol/kg intravenously) on the changes in MAP and heart rate was determined in 12-week-old male anaesthetized Sprague-Dawley rats subjected to pretreatment with either the nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME; 0.7 mg/ml by mouth for 5 days), or vehicle (control).
Ghrelin produced a significant decrease in MAP at 20 min (P < 0.05) after infusion in the control group, without any change in heart rate. The MAP recovered partially over 1 h. The ghrelin-evoked decrease in MAP was much greater (P < 0.01) and was sustained for 1 h in rats subjected to NOS inhibition. Pretreatment with the cyclo-oxygenase inhibitor, indomethacin, failed to affect the responses in either group. Intravenous infusion of 50 mug/kg each of apamin and charybdotoxin (ChTX), a combination that is known to block Ca-activated K channels or the endothelium-derived hyperpolarization process, attenuated the decrease in MAP evoked by ghrelin in both control and NOS-inhibited rats. A sodium nitroprusside-induced decrease in MAP was unaffected in the presence of apamin-ChTX, but acetylcholine-evoked hypotension was significantly reduced in both groups.
These data suggest that the Ca-activated, K-channel-mediated, ghrelin-evoked decrease in MAP may be significant in states of endothelial dysfunction associated with reduced nitric oxide availability.
研究输注生长激素促分泌素肽——胃饥饿素后平均动脉压（MAP）下降而心率无变化这一现象的潜在机制。
在12周龄雄性麻醉的Sprague-Dawley大鼠中，测定单次静脉推注胃饥饿素（12 nmol/kg）对MAP和心率变化的影响，这些大鼠预先用一氧化氮合酶（NOS）抑制剂N-硝基-L-精氨酸甲酯（L-NAME；0.7 mg/ml口服5天）或赋形剂（对照）进行预处理。
在对照组中，输注胃饥饿素后20分钟MAP显著下降（P < 0.05），心率无变化。MAP在1小时内部分恢复。在接受NOS抑制的大鼠中，胃饥饿素引起的MAP下降幅度更大（P < 0.01）且持续1小时。用环氧化酶抑制剂吲哚美辛预处理未能影响两组的反应。静脉输注50 μg/kg的蜂毒明肽和卡律蝎毒素（ChTX）（已知该组合可阻断钙激活钾通道或内皮源性超极化过程）可减弱对照组和NOS抑制组大鼠中胃饥饿素引起的MAP下降。硝普钠引起的MAP下降在存在蜂毒明肽-卡律蝎毒素的情况下不受影响，但两组中乙酰胆碱引起的低血压均显著降低。
这些数据表明，钙激活、钾通道介导的胃饥饿素引起的MAP下降在与一氧化氮可用性降低相关的内皮功能障碍状态中可能具有重要意义。
