Biomedical subjects

WenHui Wang

Publications and source records attributed to WenHui Wang.

5 recordsLinked to original sources

PubMed2004

Vascular CO counterbalances the sensitizing influence of 20-HETE on agonist-induced vasoconstriction.

We examined the influence of interactions between CO and 20-hydroxyeicosatetraenoic acid (20-HETE) on vascular reactivity to phenylephrine and vasopressin. Renal interlobar arteries incubated in Krebs buffer released CO at a rate that is decreased (from 125.0+/-15.2 to 46.3+/-8.8 pmol/mg protein per hour, P<0.05) by the heme oxygenase inhibitor chromium mesoporphyrin (CrMP; 30 micromol/L). The level of 20-HETE in vessels was not affected by CrMP (74.3+/-6.1 versus 72.5+/-16.2 pmol/mg protein), but was decreased (P<0.05) by CO (1 micromol/L; 33.2+/-7.9 pmol/mg protein) or the cytochrome P450-4A inhibitor N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS; 30 micromol/L; 11.4+/-3.3 pmol/mg protein). Phenylephrine elicited development of isometric tension in vascular rings mounted on a wire-myograph (EC(50), 0.29+/-0.02 micromol/L; R(max), 3.78+/-0.19 mN/mm). The sensitivity to phenylephrine was decreased (P<0.05) by CO (1 micromol/L; EC(50), 0.60+/-0.04 micromol/L) or DDMS (EC(50), 0.71+/-0.12 micromol/L) and increased (P<0.05) by 20-HETE (10 micromol/L; EC(50), 0.08+/-0.02 micromol/L) or CrMP (EC(50), 0.11+/-0.02 micromol/L). Notably, neither CO nor CrMP changed the sensitivity to phenylephrine in vessels treated with DDMS. Refractoriness to CO and CrMP in such a setting was eliminated by inclusion of 20-HETE (1 micromol/L) in the bathing buffer. The aforementioned interventions affected the vascular reactivity to vasopressin in a similar manner. These data indicate that the reactivity of renal arteries to phenylephrine and vasopressin is reciprocally influenced by CO and 20-HETE of vascular origin and that CO desensitizes the vascular smooth muscle to constrictor agonists by interfering with the sensitizing influence of 20-HETE.

Adrenergic Agonists↗

PubMed2004

Renal potassium channels: recent developments.

PURPOSE OF REVIEW: A variety of K+ channels have been identified with the patch-clamp technique and molecular cloning in the kidney. However, it is still a challenging task to determine the location and function of the cloned K+ channels in the corresponding nephron segment. The aim of the present review is to update the recent developments regarding the location and function of the cloned K+ channels in the native tubule. Also, the review describes the new regulatory mechanism of renal outer-medullary K (ROMK) channels and the role of Ca(2+)-activated maxi K+ channels in flow-dependent K+ secretion. RECENT FINDINGS: Several types of voltage-gated K+ (Kv) channel, such as KCNQ1, KCNA10 and Kv1.3, are highly expressed at the apical membrane of proximal tubules and distal tubules. They may participate in stabilizing the cell membrane potential. Moreover, studies performed in ROMK-knockout mice have shown that the apical 70 pS K+ channel is absent in the thick ascending limb in these mice, suggesting that the ROMK channel is also involved in forming the apical 70 pS K+ channel in the thick ascending limb. Three important kinases, protein tyrosine kinase, serum- and glucocorticoid-inducible kinase and with-no-lysine kinase, have been suggested to regulate the ROMK channel density in the cortical collecting duct. Low K+ intake increases protein tyrosine kinase expression and tyrosine phosphorylation of ROMK channels. Coexpression of with-no-lysine kinase with the ROMK channel decreases K+ current whereas serum- and glucocorticoid-inducible kinase 1 stimulates the ROMK current in oocytes in the presence of Na/H exchanger regulatory factor 2. The Ca-activated maxi K+ channel has been shown to be activated by an increase in flow rate in the rabbit cortical collecting duct. SUMMARY: The voltage-gated K+ channels are expressed in a variety of nephron segments and play a role in stabilization of cell membrane potential. With-no-lysine kinase and serum- and glucocorticoid-inducible kinase 1 have been shown to regulate ROMK1 channels. Protein tyrosine kinase mediates the effect of K+ intake on K+ secretion by stimulation of tyrosine phosphorylation of ROMK1 channels. The Ca-activated maxi K+ channel plays a role in flow-dependent K+ secretion in the distal nephron.

Animals↗

PubMed2004

Regulation of renal K transport by dietary K intake.

Extracellular K must be kept within a narrow concentration range for the normal function of neurons, skeletal muscle, and cardiac myocytes. Maintenance of normal plasma K is achieved by a dual mechanism that includes extrarenal factors such as insulin and beta-adrenergic agonists, which stimulate the movement of K from extracellular to intracellular fluid and modulate renal K excretion. Dietary K intake is an important factor for the regulation of K secretion: An increase in K intake stimulates secretion, whereas a decrease inhibits K secretion and enhances absorption. This effect of changes in dietary K intake on tubule K transport is mediated by aldosterone-dependent and -independent mechanisms. Recently, it has been demonstrated that the protein tyrosine kinase (PTK)-dependent signal transduction pathway is an important aldosterone-independent regulatory mechanism that mediates the effect of altered K intake on K secretion. A low-K intake stimulates PTK activity, which leads to increase in phosphorylation of cloned inwardly rectifying renal K (ROMK) channels, whereas a high-K intake has the opposite effect. Stimulation of tyrosine phosphorylation also suppresses K secretion in principal cell by facilitating the internalization of apical K channels in the collecting duct.

Animals↗

PubMed2003

Activity of the basolateral K+ channels is coupled to the Na+-K+-ATPase in the cortical collecting duct.

Microelectrode and patch-clamp techniques were used in the isolated cortical collecting duct to study the effects of stimulating Na+-K+-ATPase by raising bath K+ (Fujii Y and Katz AI. Am J Physiol Renal Fluid Electrolyte Physiol 257: F595-F601, 1989 and Muto S, Asano Y, Seldin D, and Giebisch. Am J Physiol Renal Physiol 276: F143-F158, 1999) on the transepithelial (VT) and basolateral membrane (VB) voltages and basolateral K+ channel activity. Increasing bath K+ from 2.5 to 8.5 mM resulted in an initial hyperpolarization of both VT and VB followed by a delayed depolarization. The effects of raising bath K+ on VT and VB were attenuated by decreasing luminal Na+ from 146.8 to 14.0 mM and were abolished by removal of luminal Na+, whereas those were magnified in desoxycorticosterone acetate (DOCA)-treated rabbits. Increasing bath K+ also led to a significant reduction of the intracellular Na+ and Ca2+ concentrations. The transepithelial conductance (GT) or fractional apical membrane resistance (fRA) were unaltered during the initial hyperpolarization phase, whereas, in the late depolarization phase, there were an increase in GT and a decrease in fRA, both of which were attenuated in the presence of low luminal Na+ (14.0 mM). In tubules from DOCA-treated animals, bath Ba2+ not only caused a significantly larger initial hyperpolarization of VT and VB but also blunted the late depolarization by high bath K+. Nomega-nitro-l-arginine methyl ester (l-NAME) partially mimicked the effect of Ba2+ and decreased the amplitude of the late depolarization. Patch-clamp experiments showed that raising bath K+ from 2.5 to 8.5 mM resulted in an increased activity of the basolateral K+ channel, which was absent in the presence of l-NAME. We conclude that stimulation of Na+-K+-ATPase increases the basolateral K+ conductance and that this effect involves suppression of nitric oxide-dependent inhibition of K+ channels.

Animals↗

PubMed2002

Absence of small conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter's) knockout mice.

The ROMK (Kir1.1; Kcnj1) gene is believed to encode the apical small conductance K(+) channels (SK) of the thick ascending limb (TAL) and cortical collecting duct (CCD). Loss-of-function mutations in the human ROMK gene cause Bartter's syndrome with renal Na(+) wasting, consistent with the role of this channel in apical K(+) recycling in the TAL that is crucial for NaCl reabsorption. However, the mechanism of renal K(+) wasting and hypokalemia that develop in individuals with ROMK Bartter's syndrome is not apparent given the proposed loss of the collecting duct SK channel. Thus, we generated a colony of ROMK null mice with approximately 25% survival to adulthood that provides a good model for ROMK Bartter's syndrome. The remaining 75% of null mice die in less than 14 days after birth. The surviving ROMK null mice have normal gross renal morphology with no evidence of significant hydronephrosis, whereas non-surviving null mice exhibit marked hydronephrosis. ROMK protein expression was absent in TAL and CCD from null mice but exhibited normal abundance and localization in wild-type littermates. ROMK null mice were polyuric and natriuretic with an elevated hematocrit consistent with mild extracellular volume depletion. SK channel activity in TAL and CCD was assessed by patch clamp analysis in ROMK wild-type ROMK(+/+), heterozygous ROMK(+/-), and null ROMK(-/-) mice. In 313 patches with successful seals from the three ROMK genotypes, SK channel activity in ROMK (+/+ and +/-) exhibited normal single channel kinetics. The expression frequencies are as follows: 67 (TAL) and 58% (CCD) in ROMK(+/+); about half that of the wild-type in ROMK(+/-), being 38 (TAL) and 25% (CCD); absent in both TAL or CCD in ROMK(-/-) between 2 and 5 weeks in 15 mice (61 and 66 patches, respectively). The absence of SK channel activity in ROMK null mice demonstrates that ROMK is essential for functional expression of SK channels in both TAL and CCD. Despite loss of ROMK expression, the normokalemic null mice exhibited significantly increased kaliuresis, indicating alternative mechanisms for K(+) absorption/secretion in the nephron.

Aging↗