Suzuki Y, Kasai K, Takekoshi K, Oka M, Banba N, Numao T, Sugimura H, Iizuka M, Shimoda S
Department of Endocrinology, Internal Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Regul Pept. 1993 Sep 3;47(2):213-20. doi: 10.1016/0167-0115(93)90426-9.
The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system were examined. When PACAP-38 (270 or 420 pmol/kg body weight) was administered intravenously to the anesthetized dogs, both mean arterial pressure and left ventricular systolic pressure increased within 2 min after a temporal depression. Pulmonary arterial systolic pressure increased promptly. These hemodynamic values and heart rates (HR) 5 min after injection were significantly higher than the corresponding values in physiological saline injected dogs, and some effects were still sustained over 15 min. Cardiac output and stroke volume also increased and the values at 5 min were significantly higher than those in controls. The high dose of PACAP-38 (420 pmol/kg) evoked greater responses than those induced by the low dose (270 pmol/kg). Plasma adrenaline, but neither noradrenaline nor dopamine concentration significantly increased 15 min after injection of 420 pmol/kg PACAP-38. Moreover, PACAP-38 clearly stimulated cyclic AMP production in rat cardiac myocytes with EC50 of 1.5 x 10(-9) M and plasma cAMP levels significantly and dose-dependently increased in dogs 5 min after administration. These results first demonstrated that PACAP has inotropic and chronotropic actions on the heart possibly by a direct stimulation of adenylate cyclase in cardiac myocytes and also that the cardiovascular functions may be possibly modified by an evoked adrenaline secretion in vivo.
研究了垂体腺苷酸环化酶激活多肽（PACAP）对心血管系统的影响。当向麻醉犬静脉注射PACAP - 38（270或420 pmol/kg体重）时，平均动脉压和左心室收缩压在短暂下降后2分钟内升高。肺动脉收缩压迅速升高。注射后5分钟时，这些血流动力学值和心率（HR）显著高于注射生理盐水的犬的相应值，且一些效应在15分钟后仍持续存在。心输出量和每搏输出量也增加，5分钟时的值显著高于对照组。高剂量的PACAP - 38（420 pmol/kg）比低剂量（270 pmol/kg）引起的反应更大。注射420 pmol/kg PACAP - 38后15分钟，血浆肾上腺素浓度显著升高，而去甲肾上腺素和多巴胺浓度均未显著升高。此外，PACAP - 38能明显刺激大鼠心肌细胞中环磷酸腺苷（cAMP）的产生，其半数有效浓度（EC50）为1.5×10⁻⁹ M，给药后5分钟犬血浆cAMP水平显著且呈剂量依赖性升高。这些结果首次表明，PACAP可能通过直接刺激心肌细胞中的腺苷酸环化酶而对心脏具有正性肌力和变时作用，并且在体内诱发的肾上腺素分泌可能会改变心血管功能。
