BACKGROUND We recently demonstrated that the sarcolemmal ATP-sensitive potassium (sarcK(ATP)) channel plays a key role in cardioprotection against ischemia/reperfusion injuries in Kir6.2-knockout (KO) mice. In the present study, we evaluated the effects of diazoxide, a mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel opener, on ischemia-induced myocardial stunning in sarcK(ATP) channe...

Pharmacological modulation of ATP-sensitive potassium channels has become a promising new therapeutic approach for the treatment of neurodegenerative diseases due to their role in mitochondrial and cellular protection. For instance, diazoxide, a well-known ATP-sensitive potassium channel activator with high affinity for mitochondrial component of the channel has been proved to be effective in a...

1 of 2 DESCRIPTION A 3-year-old boy with Down’s syndrome with no underlying cardiac anomalies presented with hypoglycaemia due to congenital hyperinsulinism (CHI). He received treatment with oral diazoxide (Proglycem) (10 mg/kg/day), along with the diuretic chlorothiazide, which ensured glycaemic stability. However, a large pericardial effusion ( fi gure 1A ) requiring drainage was noted within...

Modulation of mitochondrial respiratory chain, dehydrogenase, and nucleotide-metabolizing enzyme activities is fundamental to cellular protection. Here, we demonstrate that the potassium channel opener diazoxide, within its cardioprotective concentration range, modulated the activity of flavin adenine dinucleotide-dependent succinate dehydrogenase with an IC50 of 32 microM and reduced the rate ...

BACKGROUND Hypothermic circulatory arrest includes a remarkable risk for neurological injury. Diazoxide, a mitochondrial adenosine triphosphate-dependent potassium ion (K+ATP) channel opener, is known to have cardioprotective effects. We assessed its efficacy in preventing ischemic injury in a clinically relevant animal model. Methods: Eighteen piglets were randomized into a diazoxide group (n ...

In previous reports,'j2 we described studies of the effects of diazoxide, given in combination with trichlormethiazide, on plasma insulin and blood glucose levels in healthy subjects and in patients with functioning islet cell tumors of the pancreas. From these studies, we have concluded: ( a ) that decreased insulin secretion, as well as a failure of appropriate increases in insulin secretion,...

Protein kinase C (PKC) is involved in the second messenger signaling cascade during ischemic and Ca(2+) preconditioning. Given that the pharmacological activation of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels also mimics preconditioning, the mechanisms linking PKC activation and mitoK(ATP) channels remain to be established. We hypothesize that PKC activity is important for the openi...

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...

OBJECTIVE Mitochondrial depolarization after ATP-sensitive potassium channel activation has been shown to induce cerebral vasodilation by the generation of calcium sparks in smooth muscle. It is unclear, however, whether mitochondrial depolarization in endothelial cells is capable of promoting vasodilation by releasing vasoactive factors. Therefore, we studied the effect of endothelial mitochon...