174: Effects of ICM-I-136, a Novel Sodium (NA) Channel Blocker, on Detrusor Overactivity and Sodium Currents from Bladder Afferents

This study characterizes isometric force development in response to ouabain and K+-free solution in isolated aortic strips from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR aortas were more sensitive to ouabain than those from WKY (threshold: SHR, 3.1 X 10(-5) M; WKY, 25.6 X 10(-5) M), and force development in response to 10(-3) M ouabain was greater in SHR (SHR, 586 +/- 51 mg; WKY, 245 +/- 24 mg). Monensin, a Na+ ionophore, potentiated contractile responses to ouabain, whereas amiloride, a Na+ channel blocker, and low Na+ solutions depressed contractile responses to ouabain. Contractile responses of SHR aortic strips to K+-free solution were faster than those of WKY aortic strips [time to half-maximal response (t1/2): SHR, 24 +/- 5 min; WKY, 47 +/- 4 min]. Maximal force development by aortic strips from SHR in response to K+-free solution was not different from that of WKY aortic strips (SHR, 808 +/- 34 mg; WKY, 750 +/- 37 mg). Monensin (10(-5) M) increased the rate of force development to K+-free solution to a greater extent in WKY aortic strips than in those from SHR (t1/2: SHR, 3 +/- 1 min; WKY, 4 +/- 2 min). Amiloride and low Na+ solution depressed contractile responses to K+-free solution in both SHR and WKY aortic strips. These observations demonstrate that SHR aortas are more responsive to ouabain and K+-free solution compared with WKY aortas. Contractile responses to ouabain and K+-free solution were sensitive to experimental interventions that alter transmembrane Na+ movements.(ABSTRACT TRUNCATED AT 250 WORDS)

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Different Effect of the Pure Na+ Channel-Blocker Pilsicainide on the ST-Segment Response in the Right Precordial Leads in Patients With Normal Left Ventricular Function

Circulation Journal ◽

10.1253/circj.71.57 ◽

2007 ◽

Vol 71 (1) ◽

pp. 57-62 ◽

Cited By ~ 16

Author(s):

Takeshi Ueyama ◽

Akihiko Shimizu ◽

Toshihiko Yamagata ◽

Masahiro Esato ◽

Masato Ohmura ◽

...

Keyword(s):

Left Ventricular Function ◽

Ventricular Function ◽

Channel Blocker ◽

Left Ventricular ◽

Na Channel ◽

Normal Left Ventricular Function ◽

Normal Left Ventricular ◽

St Segment ◽

The Right

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Inhibition by extracellular Na+ replacement of GRF-induced GH secretion from rat pituitary cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.254.4.e476 ◽

1988 ◽

Vol 254 (4) ◽

pp. E476-E481 ◽

Cited By ~ 1

Author(s):

M. Kato ◽

M. A. Hattori ◽

M. Suzuki

Keyword(s):

Anterior Pituitary ◽

Channel Blocker ◽

Na Channel ◽

Pituitary Cells ◽

Ionic Mechanism ◽

Camp Production ◽

Normal Medium ◽

Gh Secretion ◽

Rat Pituitary ◽

Rat Pituitary Cells

To further clarify the ionic mechanism of the action of growth hormone (GH)-releasing factor (hGRF) on GH secretion, the involvement of extracellular Na+ was studied in perifused dispersed rat anterior pituitary cells. Replacing extracellular Na+ with mannitol or tris(hydroxymethyl)aminomethane (Tris+) suppressed hGRF- and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-induced GH secretion. The peak responses to a 2-min application of 1 nM hGRF were 165.0 +/- 5.6 ng/ml (normal medium, mean +/- SE), 21.2 +/- 1.4 ng/ml (Na+-free, mannitol medium), and 18.0 +/- 1.7 ng/ml (Na+-free, Tris+ medium). GH secretion induced by DBcAMP was also suppressed by Na+ replacement to less than 50% of that in normal medium. However, either 15 or 30 mM KCl-stimulated GH secretion was not markedly affected by replacement of Na+ with either compound. Tetrodotoxin, a voltage-sensitive Na+ channel blocker, had no effect on either hGRF- or excess K+-induced GH secretion. cAMP production by hGRF was not greatly affected by replacing extracellular Na+. Thus extracellular Na+ plays an important role in hGRF-induced GH secretion, especially in the process after cAMP production. The involvement of cAMP-sensitive Na+ channels in hGRF-stimulated GH secretion is discussed.

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Effects of Na channel blocker and Na/H exhanger inhibitor on Na content of ischemic heart

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)34718-3 ◽

1999 ◽

Vol 79 ◽

pp. 176

Author(s):

Kouichi Tanonaka ◽

Ayako Takasaki ◽

Satoshi Takeo

Keyword(s):

Channel Blocker ◽

Ischemic Heart ◽

Na Channel

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Mechanism of acidification along cortical distal tubule of the rat

AJP Renal Physiology ◽

10.1152/ajprenal.1994.266.2.f218 ◽

1994 ◽

Vol 266 (2) ◽

pp. F218-F226 ◽

Cited By ~ 9

Author(s):

R. Fernandez ◽

M. J. Lopes ◽

R. F. de Lira ◽

W. F. Dantas ◽

E. J. Cragoe Junior ◽

...

Keyword(s):

Channel Blocker ◽

Exchange Resin ◽

Rat Kidney ◽

Specific Inhibitor ◽

Distal Tubule ◽

Ringer Solution ◽

Na Channel ◽

Bafilomycin A1 ◽

Bicarbonate Reabsorption ◽

Distal Tubules

The cellular mechanism of luminal acidification (bicarbonate reabsorption) was studied in cortical distal tubules of rat kidney. The stopped-flow microperfusion technique was applied to early distal (ED) and late distal (LD) segments, perfused with bicarbonate Ringer solution to which specific inhibitors were added, to measure bicarbonate reabsorption [HCO3 flux (JHCO3)]. pH and transepithelial potential difference (Vt) were recorded by double-barreled H+ exchange resin/reference (1 M KCl) electrodes. Amiloride increased stationary pH and reduced Vt in both early and late segments. Hexamethylene-amiloride (HMA), a specific Na(+)-H+ exchange blocker, reduced JHCO3 in both segments (ED by 43.6 and LD by 40.3%) without affecting Vt. Benzamil, an Na(+)-channel blocker, reduced Vt by 75.9 in ED and 74.9% in LD but had no significant effect on acidification in both segments. The specific inhibitor of H(+)-ATPase, bafilomycin A1, inhibited LD JHCO3 at a concentration of 2 x 10(-7) M by 49%, but ED was inhibited by 24% only at 2 x 10(-6) M. Sch-28080, an inhibitor of gastric H(+)-K(+)-ATPase, reduced JHCO3 by 35% in LD of K(+)-depleted rats but not in control rats and had no effect on ED. These data indicate that, in ED, bicarbonate reabsorption is mediated mostly by Na(+)-H+ exchange. In LD, there is evidence for contribution of Na(+)-H+ exchange, vacuolar H(+)-ATPase, and H(+)-K(+)-ATPase (in K(+)-depleted rats) to bicarbonate reabsorption.

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