There are many reports for involvement of ATP-sensitive potassium channels in pancreatic, cardiac and vascular smooth muscle cells. This study examined the effect of single doses of K channel openers; diazoxide, minoxidil and K channel blockers; chlorpropamide, glibenclamide on serum concentration of aldosterone in male rats. Blood samples were obtained 60 minutes after drug treatment and serum...

Antiangiogenic action of (2R,3R,4S)-N"-cyano-N-(6-nitro-3,4-dihydro-hydroxy-2-methyl-2-dimethoxymethyl-2H-1-benzopyran-4yl)-N'-benzyl guanidine (KR-31372) was examined with its proapoptotic action in human umbilical vein endothelial cells (HUVECs) compared with diazoxide. KR-31372 as well as diazoxide significantly suppressed the neovascularization in mice induced by the Matrigel-containing rec...

OBJECTIVES We have shown previously that human diabetic myocardium cannot be preconditioned. Here, we have investigated the basis of this cardioprotective deficit. METHODS Right atrial sections from four patient groups-non-diabetic, insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM) receiving glibenclamide, and NIDDM receiving metformin-were subjected ...

Recessive inactivating mutations in the ABCC8 and KCNJ11 genes encoding the adenosine triphosphate-sensitive potassium (K(ATP)) channel subunit sulphonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel subunit (Kir6.2) are the most common cause of hyperinsulinaemic hypoglycaemia (HH). Most of these patients do not respond to treatment with the (K(ATP)) channel agonist diazoxide....

Dichlorvos, a synthetic organophosphate toxin, is used as pesticides. These toxins can be used as pesticides in farming and medicine for the devastation and/or elimination of ectoparasites of animals. Reports have shown that Dichlorvos generate seizure effects in various animals. Potassium channel opener is extensively used for medication of cardiovascular and other diseases. Studies have shown...

Individuals with long-standing type 1 diabetes (T1D) are at increased risk of severe hypoglycemia secondary to impairments in normal glucose counterregulatory responses (CRRs). Strategies to prevent hypoglycemia are often ineffective, highlighting the need for novel therapies. ATP-sensitive potassium (KATP) channels within the hypothalamus are thought to be integral to hypoglycemia detection an...

The pharmacokinetic disposition and antihypertensive response of bolus infusions of diazoxide, 1, 2, or 4 mg/kg over 5, 10, or 20 seconds, were examined in seven patients with chronic stable essential hypertension and mean arterial pressures (MAP) between 122 and 155 mm Hg off therapy. Maximal reductions in MAP were noted 2 minutes after each dose, and a linear correlation was obtained in all p...

The diverse signaling events following mitochondrial depolarization in neurons are not clear. We examined for the first time the effects of mitochondrial depolarization on mitochondrial function, intracellular calcium, neuronal nitric oxide synthase (nNOS) activation, and nitric oxide (NO) production in cultured neurons and perivascular nerves. Cultured rat primary cortical neurons were studied...

Extracellular signal-regulated kinases (ERKs) are key regulatory proteins that mediate cell survival, proliferation, and differentiation. Reactive oxygen species (ROS) may play a role in activation of the ERK pathway. Because mitochondria are a major source of ROS, we investigated whether mitochondria-derived ROS play a role in ERK activation. Diazoxide, a potent mitochondrial ATP-sensitive K+ ...

We tested if combining treatment with cariporide, an Na(+)/H(+) exchange inhibitor, and diazoxide, a mitochondrial ATP-sensitive K(+) (K(ATP)) channel opener, would reduce myocardial infarct size (IS) to a greater extent than either intervention alone. Four groups of rabbits were studied (n = 10 each): cariporide (0.3 mg/kg), diazoxide (10 mg/kg), both drugs, and saline control, given 15 min be...