Vascular deterioration is one of the complicating features of human and experimental diabetes. Some of the vascular changes in diabetes are related to alterations in endothelial function. In this regard, the vascular responsiveness to endothelium-dependent relaxant agents has been extensively investigated in human and animal models of diabetes. Endothelial cells relax vascular smooth muscle by releasing vasodilating substances, including nitric oxide (NO), PGI₂, and endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent relaxations have been consistently demonstrated in various vascular beds of diabetic animal models and humans. Several mechanisms of endothelial dysfunction have been reported, impaired signal transduction mechanisms, reduced substrate availability, impaired release of EDRF, increased destruction of EDRF, enhanced release of endothelium-derived constricting factors and decreased sensitivity of the vascular smooth muscle to EDRF. The principal mediators of hyperglycemia-induced endothelial dysfunction may be increased activity of the polyol pathway, activation of protein kinase C, formation of AGEs and oxidative stress. Correction of these pathways, as well as administrations of ACE inhibitors and statins may provide new therapeutic strategies in the treatment of diabetes.

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The vascular endothelium releases vasodilator substances, endothelium derived relaxing factors (EDRF ; nitric oxide, NO) and endothelium derived hyperpolarizing factor (EDHF), and endothelial dysfunction plays a key role in the pathogenesis of type 1 and type 2 diabetic vascular complications (macrovascular disease and microangiopathy). Impaired endothelium-dependent vasodilation has been demonstrated in various beds of different animal models of diabetes and in humans with type 1 and type 2 . Several mechanisms of endothelial dysfunction have been reported, including substrate ability, impaired release of NO, increased destruction of NO, decreased sensitivity of the vascular smooth muscle to NO, the decreased action of cyclic-AMP and decreased activity of cytochorome P450. The principal mediators of diabetes-associated endothelial dysfunction is increased in oxidized low density lipoprotein (LDL), endothelin-1 (ET-1), oxidative stress, and decreased action of insulin or growth factors in endothelial cells. Correction of these pathways, as well as administration of insulin sensitizer, antioxidants, cholesterol-lowering agents, ET-1 receptor antagonists have been shown to improve endothelium-dependent vasodilation in diabetes. This article synopsises the mechanisms underlying attenuated relaxation response of blood vessels to various agents in diabetic animals.

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ヒトを含めた多くの哺乳動物の子宮平滑筋細胞では妊娠・分娩の進行とともにgap junction (GJ) が発育する.GJの出現とその透過性変化は, 細胞間の構造的な結合のみならず, 電気的, 代謝的, さらには収縮活性といった機能的な面から見ても細胞間結合の調節に必要不可欠なものである.特にGJの出現と透過性の上昇による電気的細胞間結合の増加は, 子宮の局所の平滑筋細胞に発生した活動電位を子宮壁全域に伝達させ, 子宮全体として強力で同期性の高い収縮の発生へと誘導する.妊娠・分娩の進行に伴うGJの発育は子宮収縮の調節, ひいては陣痛の発来に重要な役割を果たしていると考えられる.

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Elevation of intracellular Ca²⁺ generates contractions of myometrial cells . The entry of Ca²⁺ is carried through L-type Ca²⁺ channels leading to action potentials and its openings are induced by depolarization. The membrane potential is regulated by various types of ion channels. Many studies on ion channels in myometrial cells have been presented using the patch-clamp method and molecular techniques. This review will briefly outline the prop erties and function of these channels.
L-and also T-type Ca²⁺ channel currents have been identified in human myometrial cells. Fast Na+ currents were also detected. These inward currents produce the rising phase of action potentials and are controlled by the membrane potentials. K⁺ channels play important roles in controlling the resting potential and repolarization of action potentials. Two types of voltage dependent K⁺ channel currents are known to be present in the myometrium. One is the delayed rectifier K⁺ (Kd) current which repolarizes the membrane during action potentials. The slow activating K⁺ current (IKs) was detected in Kd currents but the rapid type (IKr) was not. The other is I_A-like transient K_, (Kt) current. Ca²⁺ activated K⁺ (K_ca) channel was identified in various myometrial cells. The single channel conductance was around 200 pS and this channel should be BK_ca?. Recently, mRNA of Kir 6.1 and SUR2b, components of a ATP sensitive K⁺ channel, have been identified in rat myometrium. Both channels regulate the resting potential to keep the myometrium quies cent and are suggested to be a target of β-stimulants. The excitation of myometrial cells is propagated through gap junctions to synchronize cell contractions. The junctional conductance was measured to be seven times higher during delivery comparing with the late stage of gestation using double patch-clamp methods.
Nonselective cation channel currents have been isolated in rat myometrial cells and this channel has significant Ca²⁺ permeability. ATP enhanced ion conductance has been also observed in these preparations. Its properties are similar to those of the P2X channel in brain. Transient receptor potential channels have been identified in human myometrium and PHM1-41 cells using RT-PCR. These channels are supposed to relate to spontaneous depolarization and may be mechanisms of inhibition by MgSO_4 in tocolytic treatments. In the cells from circular myometrial layer hyperpolarizing activating inward currents have been identified, indicating relationship with pacemaker potentials . Ca²⁺ activating Cl channel was also reported to induce pacemaker activities of rat myometrial cells.

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