Hydrogen peroxide and peroxynitrite induce relaxations via ATP-sensitive K+ channels, indicating that oxygen-derived free radicals may activate these channels. Levels of free radicals are increased throughout the arterial wall in animal models of atherosclerosis, and therefore, vasorelaxation via ATP-sensitive K+ channels may be augmented in chronic hypertension. The present study was designed ...

BACKGROUND It is generally accepted that morphine affords cardioprotection against ischemia/reperfusion injury. Inhibition of the mitochondrial permeability transition pore (MPTP) is considered an end target for cardioprotection. The aim of this study was to investigate the involvement of opioid receptors (OR) and MPTP in morphine-induced postconditioning (M-Post). METHODS Isolated rat hearts...

The relative contribution of pre- and postsynaptic mechanisms to peripheral inhibition has been analyzed in the abdominal slow flexor muscles of crayfish and lobsters. The conductance of the muscle fiber membrane may be increased to five or more times its resting value by repetitive stimulation of the peripheral inhibitory axon, and this effect accounts for all of the attenuation exerted by the...

The vasorelaxant effects of SR 47063 (4-(2-cyanimino-1, 2-dihydropyrid-1-yl)-2,2-dimethyl-6-nitr ochromene), a new K(+)-channel opener structurally related to levcromakalim, were examined in isolated human saphenous vein (HSV) and rat aorta (RA). HSV or RA rings were precontracted with either KCl or noradrenaline and cumulative relaxant concentration-response curves were obtained for SR 47063 (...

In vitro preparations of whole urinary bladders of neonatal rats exhibit prominent myogenic spontaneous contractions, the amplitude and frequency of which can be increased by muscarinic agonists. The muscarinic receptor subtype responsible for this facilitation was examined in the present experiments. Basal spontaneous contractions in bladders from 1- to 2-wk-old Sprague-Dawley rats were not af...

Farrukh, Imad S., Wei Peng, Urszula Orlinska, and John R. Hoidal. Effect of dehydroepiandrosterone on hypoxic pulmonary vasoconstriction: a Ca21-activated K1channel opener. Am. J. Physiol. 274 (Lung Cell. Mol. Physiol. 18): L186–L195, 1998.—In the present study, we investigated the effects of the naturally occurring hormone dehydroepiandrosterone (DHEA) on hypoxic pulmonary vasoconstriction (HP...

Cytoprotective properties of potassium channel openers (KCOs) have been demonstrated in several models of cell injury, mainly in ischemia-reperfusion-induced damage of cardiac muscle. The mechanism responsible for the observed cytoprotection and the relative contribution of plasma membrane or inner mitochondrial membrane potassium channels regarding the beneficial effects exerted by KCOs remain...

The mitochondrial KATP channel (mitoKATP) is hypothesized to be the receptor for the cardioprotective effects of K+ channel openers (KCO) and for the blocking of cardioprotection by glyburide and 5-hydroxydecanoate (5-HD). Studies on glyburide have indicated that this drug is inactive in isolated mitochondria. No studies of the effects of 5-HD on isolated mitochondria have been reported. This p...

H(2)S has been proposed as physiological important molecule. It is considered as first endogenous gaseous K(+) channel opener. K(+) ATP channel activity is mainly responsible for insulin secretion. K(+)ATP channel opening of β cells leads to inhibition of insulin secretion and channels closing leads to secretion. H2S is the gaseous K(+) ATP channel opener but it does not have channel specificit...

The pore and gate regions of voltage-gated cation channels have been often targeted with drugs acting as channel modulators. In contrast, the voltage-sensing domain (VSD) was practically not exploited for therapeutic purposes, although it is the target of various toxins. We recently designed unique diphenylamine carboxylates that are powerful Kv7.2 voltage-gated K(+) channel openers or blockers...