Biomedical subjects

Z D Ge

Publications and source records attributed to Z D Ge.

6 recordsLinked to original sources

PubMed2000

Difference in endothelium-derived hyperpolarizing factor-mediated hyperpolarization and nitric oxide release between human internal mammary artery and saphenous vein.

BACKGROUND: The greater nitric oxide (NO) release that occurs in the internal mammary artery (IMA) when compared with the saphenous vein (SV) has been suggested by more endothelium-dependent relaxation in the IMA or measured by bioassay; however, no direct measurement of NO- or endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization has been reported. The present study measured such hyperpolarization, as well as NO release, in these vessels. METHODS AND RESULTS: IMA (n=46) and SV (n=61) segments taken from patients undergoing coronary surgery were studied in the organ chamber. Hyperpolarization (by intracellular glass microelectrode) and NO release (by NO-sensitive electrode) in response to acetylcholine and bradykinin, with and without incubation with N(G)-nitro-L-arginine, indomethacin, and oxyhemoglobin, were measured. The resting membrane potential of the smooth muscle cells from the IMA (58+/-0.8 mV; n=15) was higher than that in those from the SV (-62+/-0.9 mV; n=23; P:=0.0001). The EDHF-mediated hyperpolarization induced by acetylcholine (10(-5) mol/L: -9.4+/-1.5 mV in IMA, n=10, versus -4. 5+/-1.0 mV in SV, n=17; P:<0.01) and bradykinin (10(-7) mol/L: -10. 9+/-1.5 mV in IMA, n=8, versus -5.1+/-0.5 mV in SV, n=8; P:<0.01) and the basal release of NO (16.8+/-1.6 nmol/L in IMA, n=13, versus 9.9+/-2.8 nmol/L in SV, n=13; P:<0.001) were significantly greater in the IMA than in the SV. The duration of acetylcholine- and bradykinin-induced NO release was longer in the IMA than in the SV. CONCLUSIONS: The basal release of NO and EDHF-mediated hyperpolarization were significantly greater in the IMA than in the SV. In addition, the duration of the stimulated release of NO was longer in the IMA than in the SV. These differences may contribute to the superior long-term patency of IMA grafts.

Acetylcholine↗

PubMed2000

Comparison of University of Wisconsin and St Thomas' Hospital solutions on endothelium-derived hyperpolarizing factor-mediated function in coronary micro-arteries.

BACKGROUND: It is controversial whether coronary endothelial function is impaired after cold exposure to University of Wisconsin (UW) or St. Thomas' Hospital (ST) solution during heart transplantation. We therefore examined the effects of cold storage of coronary micro-arteries with UW or ST solution on endothelium-derived hyperpolarizing factor (EDHF)-mediated function. METHODS: Porcine and human coronary arteries were immersed in either UW or ST solution at 4 degrees C for 4 hr and then normalized in a wire myograph. RESULTS: In the rings (normalized diameter: 200-500 microM) precontracted by U46619, EDHF-mediated relaxation and hyperpolarization were initiated by bradykinin (BK) or A23187 in the presence of indomethacin and NG-nitro-L-arginine. In the human coronary arteries, the EDHF-mediated relaxation to BK was reduced by UW solution from 53.2+/-5.6% to 24.0+/-2.7% (P=0.006). The reduced EDHF-mediated relaxation occurred concurrently with the decreased hyperpolarization to BK (17.0+/-1.5 vs. 10.5+/-1.1 mV, n=10, P=0.004) or A23187 in porcine coronary arteries. In the control arteries, K+ channel blockers, either glybenclamide or tetraethylammonium reduced the EDHF-mediated relaxation. After exposure to UW solution, the EDHF-mediated relaxation was further significantly inhibited. In contrast, ST solution did not affect these responses. CONCLUSIONS: These results show that in coronary micro-arteries, UW, but not ST, solution impairs the EDHF-mediated function and inhibits the Ca2+-activated and ATP-sensitive K+ channels. Our comparative study suggests that ST solution may be superior to UW solution in preserving the EDHF-related endothelial function of coronary micro-arteries.

Adenosine↗

PubMed2000

Endothelium-dependent hyperpolarization and relaxation resistance to N(G)-nitro-L-arginine and indomethacin in coronary circulation.

OBJECTIVE: It is controversial whether endothelium-dependent relaxation resistance to inhibitors of nitric oxide (NO) and prostacyclin synthases is completely attributed to endothelium-derived hyperpolarizing factor (EDHF). This study examined NO release and K+ channels involved in endothelium-dependent relaxation and hyperpolarization resistance to N(G)-nitro-L-arginine (L-NNA) and indomethacin in coronary arteries with emphasis on the microarteries. METHODS: NO release, isometric force, and membrane potential of porcine coronary arteries were measured using a NO-specific electrode, wire myograph, and microelectrode, respectively. RESULTS: In large arteries pretreated with indomethacin, bradykinin (BK) evoked a rise in [NO] from 5.5+/-2.4 nM to 105.0+/-19.6 nM and hyperpolarization. L-NNA treatment significantly reduced the BK-stimulated rise in [NO] to 32.1+/-11.3 nM but did not affect the hyperpolarization. In the presence of indomethacin and L-NNA, U46619 contracted and depolarized (from -51+/-3 mV to -30+/-4 mV) vascular smooth muscle in microarteries. The addition of BK produced dose-dependent relaxation (maximal: 70.2+/-5.7%) and repolarization (membrane potential: -50+/-4 mV). Oxyhemoglobin eliminated indomethacin and L-NNA-resistance rise in [NO] but not relaxation (42.3+/-4.4%) and repolarization (-40+/-2 mV) by BK. Tetraethylammonium, charybdotoxin, and iberiotoxin partially decreased the BK-induced responses. Apamin alone did not affect the relaxation by BK; however, in combination with charybdotoxin it almost completely abolished the BK-induced relaxation and hyperpolarization. CONCLUSIONS: In porcine coronary arteries, both EDHF and NO contribute to BK-induced relaxation resistance to indomethacin and L-NNA. Large conductance Ca2+-activated K+ channels (BK(Ca)) may play an important role in mediating the BK-induced responses and small conductance Ca2+-activated K+ channels might function as 'backup' mechanisms when BK(Ca) is curtailed.

Animals↗

PubMed2000

Effect of nitric oxide on calcium-induced calcium release in coronary arterial smooth muscle.

The present study was designed to determine whether nitric oxide (NO)-induced reduction of [Ca(2+)](i) is associated with Ca(2+)-induced Ca(2+) release (CICR) in coronary arterial smooth muscle cells (CASMCs). Caffeine was used as a CICR activator to induce Ca(2+) release in these cells. The effects of NO donor, sodium nitroprusside (SNP), on caffeine-induced Ca(2+) release were examined in freshly dissociated bovine CASMCs using single cell fluorescence microscopic spectrometry. The effects of NO donor on caffeine-induced coronary vasoconstriction were examined by isometric tension recordings. Caffeine, a CICR or ryanodine receptor (RYR) activator, produced a rapid Ca(2+) release with a 330 nM increase in [Ca(2+)](i). Pretreatment of the CASMCs with SNP, CICR inhibitor tetracaine or RYR blocker ryanodine markedly decreased caffeine-induced Ca(2+) release. Addition of caffeine to the Ca(2+)-free bath solution produced a transient coronary vasoconstriction. SNP, tetracaine and ryanodine, but not guanylyl cyclase inhibitor, ODQ, significantly attenuated caffeine-induced vasoconstriction. These results suggest that CICR is functioning in CASMCs and participates in the vasoconstriction in response to caffeine-induced Ca(2+) release and that inhibition of CICR is of importance in mediating the vasodilator response of coronary arteries to NO.

Animals↗

PubMed1999

Altered endothelium-derived hyperpolarizing factor-mediated endothelial function in coronary microarteries by St Thomas' Hospital solution.

OBJECTIVES: We examined the effect of St Thomas' Hospital solution on endothelium-derived hyperpolarizing factor-mediated function in the porcine coronary microarteries with emphasis on the effect of temperature and washout time. METHODS: Microartery rings (diameter, 200-450 micrometers) were studied in myograph. The arteries were incubated in St Thomas' Hospital or Krebs solution (control) at 4 degrees C for 4 hours followed by 45 minutes (group Ia) or 90 minutes washout (group Ib) or at 22 degrees C for 1 hour followed by 45 minutes (group IIa) or 90 minutes washout (group IIb) and precontracted with -8.5 log M U 46619. The endothelium-derived hyperpolarizing factor-mediated relaxation to bradykinin was studied when endothelium-derived nitric oxide and prostaglandin I2 were inhibited with the presence of 7 micromol/L indomethacin and 300 micromol/L NG-nitro-L -arginine. RESULTS: After exposure to St Thomas' Hospital solution, the maximal endothelium-derived hyperpolarizing factor-mediated relaxation (percentage of the precontraction) was significantly reduced at either temperature after washout for 45 minutes (group Ia, 42.7% +/- 3.5% vs 69.0% +/- 5.3%; n = 9; P =.000; and group IIa, 12.3% +/- 1.6% vs 56.1% +/- 4. 4%; n = 8; P =.000) but fully recovered after washout for 90 minutes. The U46619-induced contraction force was also significantly reduced after washout for 45 minutes (P <.001) but fully recovered at 90 minutes. CONCLUSIONS: Under profound and moderate hypothermia, St Thomas' Hospital solution impairs endothelium-derived hyperpolarizing factor-mediated relaxation and smooth muscle contraction in the coronary microarteries. These effects exist during the reperfusion period for at least 45 minutes after exposure to St Thomas' Hospital solution and may account for the possible myocardial dysfunction during reperfusion.

Animals↗

PubMed1991

[Radioligand assay of beta adrenoceptors in lymphocytes isolated from rat spleen].

[3H]Dihydroalprenolol ([3H]DHA) was used to label beta-adrenoceptors in intact lymphocytes isolated from rat spleen. The binding conditions were investigated by the methods of L9 (3(4)) orthogonal analysis, the results showed the optimum binding conditions were pH 7.7, 1 x 10(8) lymphocytes.ml-1 and 10 min at 25 degrees C for incubation. On these conditions the [3H]DHA binding to beta-adrenoceptors was rapid (T1/2 2 min) and readily reversed by propranolol 1 mmol.L-1 (T1/2 4 min). [3H]DHA saturation experiments indicated a single class of site with a KD of 7.2 +/- 2.2 nmol.L-1 and Bmax of 81 +/- 28 fmol/10(7) lymphocytes (n = 3). Computer analysis of competition experiments with isoproterenol and epinephrine revealed two classes of sites. One site had high affinity for the [3H]DHA and comprised 60 +/- 5% of the total number of sites, whereas the other site had a lower affinity. The affinity of the high affinity site was about 3 orders of magnitude higher than that of the lower affinity site.

Animals↗