OBJECTIVES To examine the effect of diazoxide on hypoxia-induced soluble fms-like tyrosin kinase-1 (sFlt-1) release in JEG-3 choriocarcinoma cells. METHODS Cells were cultured under normoxia (20% O2) or hypoxia (1% O2), and expression of sFlt-1 mRNA and protein release was determined by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) assays and enzyme-linked i...

The disposition and systemic vascular effects of bolus intravenous doses of diazoxide (3.75,7.5, and 15.0 mg/kg) were studied in anesthetized open-chest dogs. Blood flow (0) and right atrial pressure (Pra) were independently controlled by a right heart bypass. The late phase disposition halflife (beta t Vt) of diazoxide averaged 3.4 ± 0.5 hrs (x ± SEM) with an apparent volume of distribution at...

background: diazoxide is the main therapeutic agent for congenital hyperinsulinism. the drug is generally well tolerated; however, in this report severe adverse effects including heart failure (hf) and pulmonary hypertension (ph) in an infant are reported.case report: a sixteen-day male infant with persistent hypoglycemia and with diagnosis of congenital hyperinsulinism underwent near total pan...

Similar to ischemic preconditioning, diazoxide was documented to elicit beneficial bioenergetic consequences linked to cardioprotection. Inhibition of ATPase activity of mitochondrial F(0)F(1) ATP synthase may have a role in such effect and may involve the natural inhibitor protein IF(1). We recently documented, using purified enzyme and isolated mitochondrial membranes from beef heart, that di...

Ethanol-induced acute gastric ulceration (EIGU) is widely studied. ATP dependent potassium channel (KATP) modulators are thought to interfere with some physiologic functions of the stomach. We have studied the effects of different doses of KATP modulators (diazoxide as agonist and glibenclamide as antagonist) on EIGU in rats. Gastric lesions were quantified. Fasting blood glucose (FBS) levels w...

The mitochondrial ATP-sensitive K(+) (mitoKATP) channel plays a significant role in mitochondrial physiology and protects against ischemic reperfusion injury in mammals. Although fish frequently face oxygen fluctuations in their environment, the role of the mitoKATP channel in regulating the responses to oxygen stress is rarely investigated in this class of animals. To elucidate whether and how...

BACKGROUND Ischemic preconditioning accelerates suppression of gap junction (GJ) permeability during myocardial ischemia, and GJ blockers reduce infarct size. We hypothesized that the mitochondrial ATP-sensitive K+ (mitoKATP) channel is one of the mechanisms regulating GJ permeability through the mitogen-activated protein kinase ERK, leading to cardioprotection. METHODS AND RESULTS In isolate...

Seven infants with persistent neonatal hyperinsulinism were treated in Dhahran Health Centre from 1983 to 1986. The insulin:glucose ratio (serum insulin concentration pmol/l) divided by the blood glucose concentration (mmol/l) ranged from 12 to 636, mean (SD) 177 (201). To control hypoglycaemia, diazoxide (12-24 mg/kg/day) was given in a continuous intravenous glucose infusion (12-22 mg/kg/min)...

Diazoxide was administered to sixteen pediatric patients (ages 10 months to 13 years) with secondary forms of hypertension. Admission BP was 178+/-8/130+/-5 mm Hg (mean +/- SEM). Diazoxide was administered rapidly intravenously in doses ranging from 2 to 7.5 mg/kg. A significant (P less than 0.001), linear log dose-response relation was obtained which showed that a 3 mg/kg dose of diazoxide low...

This study aimed to use long-term diazoxide treatment to establish a loss-of-cardioprotection model and then perform proteomics analysis to explore which proteins of mitochondrial inner membrane (MIM) are potentially involved in delayed cardioprotection. Rats received 1 to 8 weeks of diazoxide treatments (20 mg•kg-1•d-1) to establish a loss-of-cardioprotection model in different groups. Detecti...