Ohashi M, Dohi Y, Itoh T
Department of Pharmacology, Nagoya City University Medical School, Mizuho-Ku, Nagoya 467-8601, Japan.
Br J Pharmacol. 2000 Mar;129(5):1000-6. doi: 10.1038/sj.bjp.0703125.
The possible mechanisms underlying the vasodilatation induced by olprinone, a phosphodiesterase type III inhibitor, were investigated in smooth muscle of the rabbit coronary artery. Isometric force and membrane potential were measured simultaneously using endothelium-denuded smooth muscle strips. Acetylcholine (ACh, 3 microM) produced a contraction with a membrane depolarization (15. 2+/-1.1 mV). In a solution containing 5.9 mM K(+), olprinone (100 microM) hyperpolarized the resting membrane and (i) caused the absolute membrane potential level reached with ACh to be more negative (but did not reduce the delta membrane potential seen with ACh, 15.2+/-1.8 mV) and (ii) attenuated the ACh-induced contraction. In a solution containing 30 mM K(+), these effects were not seen with olprinone. Glibenclamide (10 microM) blocked the olprinone-induced membrane hyperpolarization. 4-AP (0.1 mM) significantly attenuated the olprinone-induced resting membrane hyperpolarization but TEA (1 mM) had no such effect. Glibenclamide (10 +microM), TEA (1 mM) and 4-AP (0.1 mM), given separately, all failed to modify the inhibitory actions of olprinone on (i) the absolute membrane potential level seen with ACh and (ii) the ACh-induced contraction. It is suggested that olprinone inhibits the ACh-induced contraction through an effect on the absolute level of membrane potential achieved with ACh in smooth muscle of the rabbit coronary artery. It is also suggested that glibenclamide-sensitive, ATP-sensitive K(+) channels do not play an important role in the olprinone-induced inhibition of the ACh-induced contraction.
在兔冠状动脉平滑肌中研究了磷酸二酯酶III型抑制剂奥普力农诱导血管舒张的潜在机制。使用去内皮的平滑肌条同时测量等长力和膜电位。乙酰胆碱（ACh，3μM）引起收缩并伴有膜去极化（15.2±1.1 mV）。在含有5.9 mM K⁺的溶液中，奥普力农（100μM）使静息膜超极化，并且（i）使ACh达到的绝对膜电位水平更负（但未降低ACh引起的膜电位变化，15.2±1.8 mV），以及（ii）减弱ACh诱导的收缩。在含有30 mM K⁺的溶液中，奥普力农未出现这些作用。格列本脲（10μM）阻断了奥普力农诱导的膜超极化。4-氨基吡啶（0.1 mM）显著减弱了奥普力农诱导的静息膜超极化，但四乙铵（1 mM）没有这种作用。单独给予格列本脲（10μM）、四乙铵（1 mM）和4-氨基吡啶（0.1 mM）均未能改变奥普力农对（i）ACh所见的绝对膜电位水平和（ii）ACh诱导的收缩的抑制作用。提示奥普力农通过影响兔冠状动脉平滑肌中ACh所达到的膜电位绝对水平来抑制ACh诱导的收缩。还提示格列本脲敏感的ATP敏感性钾通道在奥普力农抑制ACh诱导的收缩中不发挥重要作用。
