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Biomedical subjects

K W Hong

Publications and source records attributed to K W Hong.

51 records · Page 3Linked to original sources
PubMed1993

Disturbances in autoregulatory responses of rat pial arteries by sulfonylureas.

It was aimed to test the role of ATP-sensitive K+ channels in the autoregulatory response of cerebral arterioles in vivo. Changes in pial arterial caliber (mean, 43.2 +/- 2.3 microns in diameter) in response to changes in systemic arterial blood pressure (mean, 104.3 +/- 1.4 mmHg) were observed directly through closed cranial windows in anesthetized normotensive rats. During superfusion with vehicle, pial arterial caliber automatically increased in response to hypotension induced by arterial bleeding into a reservoir and decreased on reverse of arterial blood pressure by infusion of blood. After pretreatment with sulfonylureas, glibenclamide (1 and 3 microM) and glipizide (30 and 100 microM), arteriolar dilatation and constriction observed during hypotension and its reverse were disturbed. A similarity was evidenced when hypotension was induced by sodium nitroprusside (750 nmol kg-1min-1, i.v.). Cromakalim, a K+ channel opener, exerted a concentration-dependent vasodilatation of the pial artery and its effect was antagonized by glibenclamide. These data suggest that the endogenous glibenclamide-sensitive K+ channel opener is involved in the modulation of cerebral microvascular autoregulation.

Animals↗
PubMed1992

Similarities between effects of superoxide-mediated endothelium-derived relaxing factor and cromakalim.

A stable endothelium-derived relaxing factor has been reported to be generated on exposure of endothelial cells to the superoxide anion. In this study, we first evaluated the effects of the relaxing factor and cromakalim on mechanical tone and, second, assessed their consequences on the 86Rb efflux rate. On application of hypoxanthine-xanthine oxidase to a bath for generating superoxide anion, the precontracted rabbit mesenteric artery exhibited another transient increase in contraction, followed by sustained relaxation. This relaxation was lost in the K(+)-physiological salt solution (PSS) (greater than 35 mM) and was inhibited by glibenclamide (10 microM) but not by N-methyl-L-arginine or methylene blue. Hypoxanthine-xanthine oxidase application did not increase either basal or stimulated synthesis of guanosine 3',5'-cyclic monophosphate. In the presence of 2 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and 10 mM MgCl2, the relaxing factor caused a significant increase in 86Rb efflux from the aortic and mesenteric arterial segments, as did the cromakalim. The increased 86Rb efflux, either by the relaxing factor or by cromakalim, was wholly inhibited by glibenclamide. These results suggest that superoxide-mediated endogenous relaxing factor may have a similar mechanism of action to cromakalim in vasodilatation.

Animals↗
PubMed1989

Release of superoxide-dependent relaxing factor(s) from endothelial cells.

In the present work, an experimental system was designed to study superoxide anion radical, implicated as the cause of vascular dilatation. To circumvent its direct effect, we employed a two-bath system. When the endothelial cells (EC) were exposed to electrical field stimulation (EFS) or to a hypoxanthine-xanthine oxidase system in bath A plus its physiological buffer solution suffused on a helical strip of cat basilar artery in bath B, the contraction to 5-hydroxytryptamine (5-HT) was depressed to approximately 40-50% of the control value. The reduction was not elicited on EFS in a state of calcium deficiency or in the absence of EC. The depression could be prevented by pretreatment with superoxide dismutase (SOD), but not with an effective dose of catalase, dimethyl sulfoxide (DMSO), mannitol, or indomethacin. The percent depression of contraction was paralleled by an increase in SOD-inhibitable cytochrome c reduction, which was not associated with cyclic guanosine 3',5'-monophosphate formation. These results suggest that superoxide-dependent relaxing factor is released from EC differently than the endothelium-derived relaxing factor mediated by acetylcholine.

Animals↗
PubMed1987

Role of central alpha 2-adrenoceptors on the development of muricidal behavior in olfactory bulbectomized rats: effect of alpha 2-adrenoceptor antagonists.

Upon surgical removal of olfactory bulbs, by the 8th to 10th day after the surgery muricidal behavior has been demonstrated in 75.4% of rats. In the homogenates of forebrain obtained from rats demonstrating muricidal behavior, levels of noradrenaline, 5-hydroxytryptamine and their metabolites (i.e., 3-methoxy-4-hydroxyphenylglycol sulfate and 5-hydroxyindoleacetic acid) were not changed. However, the fractional turnover rate of noradrenaline in the forebrain of the olfactory bulbectomized rats was significantly decreased without alterations in the metabolism of 5-hydroxytryptamine when compared to that of the sham rats. The muricidal behavior and the aggressiveness were suppressed by antagonists of alpha 2-adrenoceptors (yohimbine, idazoxan and rauwolscine), but not by the alpha 1-adrenoceptor antagonist (corynanthine). Furthermore, upon administration of yohimbine or idazoxan to rats demonstrating the muricidal behavior, the level of noradrenaline in the homogenates of forebrain was decreased while that of 3-methoxy-4-hydroxyphenylglycol sulfate was increased. The maximum binding capacity (Bmax) of [3H]yohimbine to the forebrain membranes obtained from the olfactory bulbectomized rats was significantly higher than that from the sham rats without demonstrating any differences in dissociation constants (Kd) between the two brain membranes. Based on these results, it was suggested that olfactory bulbectomy has caused some functional changes in central alpha 2-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1987

Increased alpha 1- and decreased alpha 2-adrenoceptor sensitivities upon chronic treatment with imipramine in mediating cardiovascular responses in pithed rats.

After chronic treatment with imipramine (20 mg/kg, i.p., twice daily for 14 days) the pressor dose-response curves to phenylephrine, methoxamine and cirazoline (alpha 1-adrenoceptor agonists) significantly shifted to the left with decreased PD50 values in pithed rats; however, the dose-response curve to Sgd 101/75, a selective alpha 1-adrenoceptor agonist was not affected. On the other hand, the alpha 2-adrenoceptor agonists such as B-HT 920, xylazine and clonidine produced a rightward shift for both the pressor (increased PD50) and cardioinhibition (increased ID50) dose-response curves in these rats. These results required treatment with imipramine over 2 weeks. Chronic treatment with imipramine has reduced the antagonism by prazosin of the pressor effect of phenylephrine when compared with the dose-ratios between the 2 groups. On the contrary, the antagonism by piperoxan of the cardioinhibitory effect of B-HT 920 was rather enhanced by the treatment, but that of the pressor effect of B-HT 920 was little changed. In cerebrocortical membrane fractions obtained from rats pretreated with imipramine, Ki of phenylephrine to displace [3H]prazosin was decreased, whereas that of clonidine and yohimbine to displace [3H]yohimbine was increased. In conclusion, it is demonstrated that after chronic imipramine treatment the peripheral alpha 2-adrenoceptors (both presynaptic and postsynaptic sites) as well as central alpha 2-adrenoceptors respond with a decreased sensitivity to the alpha 2-adrenoceptor agonists, and moreover, this treatment produces an increased sensitivity of the central and peripheral alpha 1-adrenoceptors to the alpha 1-adrenoceptor full agonists.

Adrenergic alpha-Antagonists↗
PubMed1986

Enhancement of central and peripheral alpha 1-adrenoceptor sensitivity and reduction of alpha 2-adrenoceptor sensitivity following chronic imipramine treatment in rats.

After chronic imipramine treatment (20 mg/kg i.p., once daily for 14 days) the dose-response curve of the isolated rat anococcygeal muscle to phenylephrine shifted to the left, and furthermore, the -log KA value (affinity) for phenylephrine was significantly increased without affecting the affinity for guanfacine. On the other hand, such treatment caused a shift to the right of the dose-response curve to guanfacine on aortic strips and the affinity of the alpha-adrenoceptor for guanfacine was lowered without any accompanying changes in the affinity value for phenylephrine. However the relative efficacies of phenylephrine or guanfacine were not influenced by imipramine in either preparation. The ability of phenylephrine to displace [3H]prazosin from its specific binding sites was significantly enhanced after chronic imipramine treatment. These results may indicate that following chronic imipramine treatment the alpha 1-adrenoceptors of both central and peripheral tissues responded with supersensitivity to an alpha 1-preferential agonist, and the alpha 2-adrenoceptors with reduced sensitivity to an alpha 2-preferential agonist.

Adrenergic alpha-Agonists↗
PubMed1985

"On" and "off" responses of guinea pig ureter.

The in vitro guinea pig ureter responds to 5-s trains of electrical stimuli with two contractions: the first, an "on" response, occurs within 0.1-0.3 s after the onset of the stimulus train; the second, an "off" response, occurs 0.2-1.0 s after the termination of the stimulus train. Force decreases between the two responses during a time when the stimulus is still being delivered. Longer duration and/or higher frequencies of stimuli within the train are required to elicit the off response than the on response. Neither the on nor the off response appears to be neurally mediated, since both responses are unchanged by tetrodotoxin, phentolamine, atropine, and pyrilamine. Decreasing temperature from 37 to 22 degrees C decreases the amplitude of the on response and increases the amplitude of the off response. Calcium-free solution, 2 mM ethylenediaminetetraacetic acid (EDTA), 1 mM Mn2+, and 1 microM verapamil abolish the on response at a time at which the off response continues to persist. Conversely, 0.5 mM caffeine and 0.1 mM theophylline abolish the off response, whereas they only slightly reduce the on response. These data suggest that the on response depends on extracellular free calcium, whereas the off response is more dependent on bound or stored calcium.

Animals↗
PubMed1980

Effect of age on contractility of guinea pig ureter.

Longitudinal force-length relationships of guinea pig ureter were studied in vitro in animals 3 weeks, 3 months, and 3 years of age. Distal segments of 3-week-olds underwent a greater per cent increase in length in response to an applied resting force than those from older age groups. Resting force-length relations of proximal segments were unaffected by age. Active force was higher in distal segments at all ages and at all lengths. Maximum active force increased with age. The increase in force developed between 3 weeks and 3 months of age seemed to be attributable to an increase in contractility since there was an associated increase in active stress; the increase developed between the 3-month- and 3-year-olds was associated with increased muscle cross-sectional area but with no change in active stress. This finding suggests that no change in contractility occurred during this time interval.

Aging↗
PubMedDate not supplied

KR 31372, a benzopyran derivative, inhibits oxidized LDL-stimulated proliferation and migration of vascular smooth muscle cells.

KR 31372 is a benzopyran derivative. Both [3H]thymidine incorporation and migrations (chemotactic and wound-edge) of cultured smooth muscle cells (SMCs) were greatly stimulated by oxidized low-density lipoprotein (LDL). These effects were significantly suppressed by KR 31372 (10(7) - 10(6) M) and PDGF-BB antibody (10(8) - 10(6) M). Preincubation with KR 31372 led to a decrease in the synthesis of PDGF-BB-like immunoreactivity (PDGF-BB-LI) that had been stimulated by oxidized LDL. Otherwise, KR 31372 and probucol strongly inhibited the production of thiobarbituric acid reactive substances (TBARS) caused by the incubation of LDL with Cu2+ ion, and significantly reduced the intracellular oxidative stress when stimulated with H,O2. Taken together, it is suggested that KR 31372 may inhibit the oxidized LDL-stimulated syntheses of DNA and PDGF-BB, and migration of the SMCs, in part, via the antioxidant activity.

Animals↗
PubMedDate not supplied

Relaxant effects of cromakalim and ATP depletion in dog and rat mesenteric arteries--species differences.

In the present study, the effects of cromakalim on tension and 86Rb+ efflux rate were evaluated in strips of dog and rat mesenteric arteries and compared with the variables obtained from ATP-depleted strips of both species. The cromakalim-induced relaxation was competitively antagonized by glibenclamide, with similar pA2 values, in both dog and rat mesenteric arteries. Glibenclamide caused an enhancement of the precontraction or a reversal of the cromakalim-induced inhibition in the mesenteric arteries of both species when cromakalim was applied prior to or during phenylephrine-contraction. The 86Rb+ efflux rate from the mesenteric arteries was significantly increased in both species after application of cromakalin (10 microM). However, in the ATP-depleted mesenteric artery (verified by high performance liquid chromatography), an increase in 86Rb+ efflux and a glibenclamide-induced enhancement of contraction were observed in the rat, but not in the dog. Taken together, between dog and rat mesenteric arterial strips, a differential effect of ATP depletion with 2-deoxyglucose plus oligomycin was identified in the activation of ATP-sensitive K+ channels, but not of cromakalim.

Adenosine Triphosphate↗
PubMedDate not supplied

Relaxation by cromakalim and pinacidil of isolated smooth muscle cells from canine coronary artery-multiple sites of action.

Dispersed cells were isolated from the canine coronary artery by enzymatic digestion. Their contraction and relaxation were determined by measuring their length using a video microscaler system. The cells remained structurally intact when examined by Trypan blue exclusion and electron microscopy. The cells showed a concentration-dependent contraction (EC50: 2.3 +/- 0.36 x 10(-12) M) to phenylephrine. The phenylephrine-induced contraction of the intact cells was inhibited by cromakalim (IC50: 1.24 +/- 0.27 x 10(-10) M) and pinacidil (IC50: 6.8 +/- 1.89 x 10(-10) M). The sensitivity of the dispersed cells to cromakalim was approximately 3 orders of magnitude larger than that of the muscle strips (EC50: 1.94 +/- 0.22 x 10(-7) M). Glibenclamide (a selective inhibitor of the ATP-sensitive K+ channel in pancreatic beta-cells) competitively antagonized the cromakalim-induced inhibition of the phenylephrine-contraction in intact cells (pA2:9.12; slope: 1.13) as well as in muscle strips (pA2: 7.84; slope: 0.95). Permeabilized cells were made by a brief exposure of the cells to saponin and were suspended in a buffer medium containing 100 mM KCl and 0.18 microM Ca++. The cells showed a concentration-dependent contraction to phenylephrine (EC50:2.2 +/- 0.40 x 10(-12) M) and inositol 1,4,5-triphosphate (EC50: 5.3 +/- 1.05 x 10(-11) M). These contractions were concentration-dependently inhibited by cromakalim and pinacidil. The inhibition by cromakalim of the inositol-induced contraction was markedly antagonized by apamin and, to a lesser extent, by glibenclamide. Thus, it is suggested that cromakalim and pinacidil exert a potent relaxation by acting on multiple sites: the glibenclamide-sensitive K+ channels of the plasma membrane and the intracellular site sensitive to inositol and apamin.

Animals↗