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G W He

Publications and source records attributed to G W He.

At least 19 recordsLinked to original sources
PubMed2004

The relaxant effect of urocortin in rat pulmonary arteries.

Urocortin is a potent vasodilator, which plays physiological or pathophysiological roles in systemic circulation. However, little is known about its action on pulmonary circulation. The present study was aimed to characterize some cellular mechanisms underlying the relaxant effect of urocortin in isolated rat pulmonary arteries. Changes in isometric tension were measured on small vessel myographs. Urocortin inhibited U46619-induced contraction with reduction of the maximal response. Urocortin-induced relaxation was independent of the presence of endothelium. Inhibitors of nitric oxide (NO)-dependent dilator, NG-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one, did not affect the relaxation. Astressin (100-500 nM), a corticotropin-releasing factor (CRF) receptor antagonist and KT5720, a protein kinase A (PKA) inhibitor reduced urocortin-induced relaxation. Urocortin produced less relaxant effect in 30 mM K+- than U46619-contracted arterial rings. Urocortin did not reduce CaCl2-induced contraction in 60 mM K+-containing solution. Ba2+ (100-500 microM) but not other K+ channel blockers reduced the relaxant responses to urocortin. Urocortin also relaxed the rings preconstricted by phorbol 12,13-diacetae in normal Krebs solution while this relaxation was less in a Ca2+-free solution. Our results show that urocortin relaxed rat pulmonary arteries via CRF receptor-mediated and PKA-dependent but endothelium/NO or voltage-gated Ca2+ channel-independent mechanisms. Stimulation of Ba2+-sensitive K+ channel may contribute to urocortin-induced relaxation. Finally, urocortin relaxed pulmonary arteries partly via inhibition of a PKC-dependent contractile mechanism.

Animals↗
PubMed2001

Comparison of nitric oxide release and endothelium-derived hyperpolarizing factor-mediated hyperpolarization between human radial and internal mammary arteries.

BACKGROUND: Arterial grafts for CABG have been used increasingly, and the radial artery (RA) has become a preferable graft, secondary to the internal mammary artery (IMA). In the present study, we investigated and compared NO release and endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization for IMA and RA. METHODS AND RESULTS: IMA and RA segments taken from CABG patients were placed in an organ chamber. An NO-sensitive electrode (to directly measure NO release) or intracellular glass microelectrode (to measure membrane potential) was used to study NO or EDHF in response to acetylcholine (ACh) and bradykinin (BK) before and after incubation with indomethacin (a cyclooxygenase inhibitor), N(G)-nitro-L-arginine (an NO synthase inhibitor), and oxyhemoglobin (an NO scavenger). The resting membrane potential of the smooth muscle cells of IMA and RA was -58+/-0.84 (n=61) and -61+/-1.3 (n=46) mV, respectively (P=0.03). BK-induced EDHF-mediated hyperpolarization in the IMA was significantly greater than that in RA (BK 10(-)(7) mol/L: -10.9+/-1.5 [n=7] versus -5.8+/-0.9 [n=6] mV, P=0.04). The basal (16.8+/-1.9 versus 11.1+/-1.0 nmol/L, n=12, P=0.02) and stimulated releases of NO in IMA were significantly greater for BK (44.3+/-4.0 versus 25.8+/-3.6 nmol/L, n=8, P=0.004) and lasting longer for ACh (9.5+/-2.0 versus 6.6+/-3.6 minutes, n=12, P=0.03) than those in RA. CONCLUSIONS: The basal and stimulated releases of NO and EDHF-mediated hyperpolarization in the IMA are significantly greater than that in the RA. The lower capacity of NO release may contribute to the susceptibility of RA to the perioperative vasospasm and may have an impact on the long-term graft patency.

Acetylcholine↗
PubMed2001

Direct measurement of nitric oxide release from saphenous vein: abolishment by surgical preparation.

BACKGROUND: Surgical preparation (distension) of the saphenous vein (SV) is applied routinely during harvesting in coronary artery bypass grafting (CABG). However, mechanical distension may impair the endothelium, which plays an important role in long-term patency. The present study investigated the effect of surgical preparation of the SV on nitric oxide (NO) release from the endothelium by direct measurement of NO. METHODS: Saphenous vein segments taken from CABG patients were cut open longitudinally and placed in an organ chamber. An NO-sensitive electrode and NO meter were used to directly measure NO release induced by acetylcholine (ACh) and bradykinin (BK) from the surgically prepared veins (PV) compared with the control (nondistended) veins. RESULTS: The basal release of NO in the PV group was significantly lower than that in the control group (3.4 +/- 1.4 nM, n = 9 versus 9.9 +/- 2.8 nM, n = 13, p = 0.002). The maximum concentrations of NO release induced by ACh and BK in the PV group were also significantly lower than those in the control veins (for ACh 10(-6) mol/L: 9.6 +/- 3.1 nM, n = 8 versus 41.9 +/- 11.2 nM, n = 12, p = 0.005; for BK 10(-8) mol/L: 8.3 +/- 3.7 nM, n = 7 versus 37.9 +/- 6.1 nM, n = 9, p = 0.003). Further, the duration of NO release in the PV group was significantly shorter than that in control veins (1.5 +/- 1.3 minutes, n = 8 versus 8.1 +/- 1.9 minutes, n = 8, p < 0.001). CONCLUSIONS: Surgical preparation almost abolishes NO release by the SV and this may significantly contribute to the low long-term patency rate of the vein graft.

Endothelium, Vascular↗
PubMed2001

Effects of potassium channel opener aprikalim on the receptor-mediated vasoconstriction in the human internal mammary artery.

BACKGROUND: Arterial grafts for coronary artery bypass grafting such as the internal mammary artery (IMA) may develop spasm perioperatively. The purpose of this study was to investigate the effects of the potassium channel opener, aprikalim, on the receptor-mediated vasoconstriction in the human IMA in vitro. METHODS: We studied 160 IMA rings taken from coronary artery surgery in organ baths. The interaction between aprikalim and four vasoconstrictors 5-hydroxytryptamine (5-HT), norepinephrine (NE), endothelin-1 (ET-1), and angiotensin II (AII) was investigated in two ways. RESULTS: Aprikalim relaxed IMA rings precontracted by the vasoconstrictors to 66.40 +/- 5.9% for 5-HT (EC50: -6.78 +/- 0.26 LogM), 57.40 +/- 5.5% for NE (-6.54 +/- 0.39 LogM), 81.00 +/- 6.7% for ET-1 (-6.58 +/- 0.26 LogM), and 93.90 +/- 2.5% for AII (-7.80 +/- 0.23 LogM). The relaxation in endothelium-denuded rings contracted by AII was similar to that in the endothelium-intact rings. The relaxation was attenuated by glibenclamide (3 microM) in 5-HT or NE-precontracted IMA. Pretreatment with aprikalim at 1 microM depressed AII-induced contraction (33.20 +/- 7.5% versus 59.70 +/- 7.3%, p < 0.01) but only shifted the curves rightward for 5-HT or NE (EC50 3.1 or 4.3-folds higher, p < 0.05), whereas at 30 microM it also significantly depressed the maximal contraction for 5-HT (35.70 +/- 4.9% versus 103.30 +/- 9.8%, p < 0.001) and NE (90.60 +/- 15.6% versus 125.60 +/- 7.9%, p < 0.05). In contrast, aprikalim did not significantly depress the contraction induced by ET-1 (p > 0.05). CONCLUSIONS: We conclude that aprikalim has vasorelaxant effects on IMA and the effect is vasoconstrictor-selective and endothelium-independent. Aprikalim may provide clinically useful vasorelaxant effects in coronary bypass surgery.

Angiotensin II↗
PubMed2001

ATP-sensitive potassium channel openers may mimic the effects of hypoxic preconditioning on the coronary artery.

BACKGROUND: This study was designed to investigate the effects of the potassium channel opener KRN4884 in mimicking hypoxic preconditioning on coronary arteries and to explore the possible mechanisms. METHODS: In the organ chamber, porcine coronary artery rings (n = 96) were studied in 6 groups (n = 16 in each group): I. CONTROL: normoxia (pO2 > 200 mmHg); II. Hypoxia-reoxygenation: 60-minute hypoxia (pO2 < 15 mmHg) followed by 30-minute reoxygenation; III. Preconditioning: 5-minute hypoxia followed by 10-minute reoxygenation prior to hypoxia-reoxygenation; IV. KRN4884-pretreatment: KRN4884 (30 microM) was added into the chamber 20 minutes before hypoxia-reoxygenation; V. 5-HD-pretreatment: sodium 5-hydroxydecanoate (5-HD, 10 microM) was given 20 minutes prior to KRN4884-pretreatment; and VI. GBC-pretreatment: glibenclamide (GBC, 3 microM) was added 20 minutes prior to KRN4884-pretreatment. Concentration-contraction curves for U46619 (n = 8 in each group) were constructed. Concentration-relaxation curves for bradykinin (n = 8 in each group) related to endothelium-derived hyperpolarizing factor (EDHF) were established in the rings precontracted with U46619 (30 microM) in the presence of Nomega-nitro-L-arginine (L-NNA, 300 microM) and indomethacin (7 microM). RESULTS: The maximal relaxation induced by bradykinin was reduced in hypoxia-reoxygenation (54.6 +/- 4.3% versus 85.2 +/- 5.7% in control, p = 0.001). This reduced relaxation was recovered in KRN4884-pretreatment (78.9 +/- 3.7%, p = 0.014) or preconditioning (79.9 +/- 3.7%, p = 0.009). 5-HD- but not GBC-pretreatment abolished the effect of KRN4884-pretreatment (78.9 +/- 3.7% versus 53.5 +/- 4.7%, p = 0.009). CONCLUSIONS: Hypoxia-reoxygenation reduces the relaxation mediated by EDHF in the coronary artery. This function can be restored by either hypoxic preconditioning or the potassium channel opener KRN4884. The mechanism of such effect is mainly related to the mitochondrial ATP-sensitive K+ channels.

Adenosine Triphosphate↗
PubMed2001

Epoxyeicosatrienoic acids (EET(11,12)) may partially restore endothelium-derived hyperpolarizing factor-mediated function in coronary microarteries.

BACKGROUND: Endothelial cells derive nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The cytochrome P-450-monooxygenase metabolites of arachidonic acid (epoxyeicosatrienoic acids [EETs]) have been suggested to be EDHF. This study was designed to examine the effect of EET(11,12) with regard to the possibility of restoring EDHF function when added into hyperkalemic cardioplegic solution. METHODS: Porcine coronary microartery rings were studied in a myograph. In groups 1 and 2, paired arteries were incubated in either hyperkalemic solution (K+ 20 mmol/L) or Krebs' solution (control). In group 3, the paired arteries were incubated in hyperkalemia plus EET(11,12) (1 x 10(-6.5) mol/L) or hyperkalemia alone (control) at 37 degrees C for 1 hour, followed by Krebs' washout and then precontracted with 1 x 10(-8.5) mol/L U46619. The EDHF-mediated relaxation to EET(11,12) (group 1) or bradykinin (groups 2 and 3) was studied in the presence of N(G)-nitro-L-arginine, indomethacin, and oxyhemoglobin. RESULTS: After exposure to hyperkalemia, the EDHF-mediated maximal relaxation by bradykinin (72.5% +/- 7.8% versus 41.6% +/- 10.6%; p < 0.05), but not by EET(11,12) (18.4% +/- 3.3% versus 25.1% +/- 4.9%; p > 0.05) was significantly reduced. Incubation with EET(11,12) partially restored EDHF function (33.3% +/- 9.5% versus 62.0% +/- 8.5%; p < 0.05). CONCLUSIONS: In coronary microarteries, hyperkalemia impairs EDHF-mediated relaxation, and EET(11,12) may partially mimic the EDHF function. Addition of EET(11,12) into cardioplegic solution may partially restore EDHF-mediated function reduced by exposure to hyperkalemia.

8,11,14-Eicosatrienoic Acid↗
PubMed2001

Inhibition of vasoconstriction by AJ-2615, a novel calcium antagonist with alpha(1)-adrenergic receptor blocking activity in human conduit arteries used as bypass grafts.

AIMS: Graft spasm may develop during coronary artery bypass grafting and reversal of spasm is still challenging. The purpose of this study was to investigate the in vitro vascular relaxant properties of AJ-2615 in human internal mammary artery (IMA). METHODS: We studied 264 IMA rings taken from 65 patients undergoing coronary artery bypass grafting surgery with organ bath technique. The interaction between AJ-2615 and various vasoconstrictors was investigated in two ways. RESULTS: AJ-2615 caused complete relaxation in methoxamine-contracted IMA rings (100.0+/-0.0%; n = 8) and nearly full relaxation in potassium chloride-contracted IMA rings (91.4+/-5.7%; n = 8) or noradrenaline-contracted IMA rings (89.3+/-2.8%; n = 8). AJ-2615 also induced remarkable relaxation in IMA rings contracted by other vasoconstrictors. In comparison with the alpha1-adrenoceptor antagonist prazosin, AJ 2615 showed similar maximal relaxation in IMA rings contracted by methoxamine or norepinephrine. On the other hand, incubation with AJ-2615 (0.1-1 microM) significantly inhibited all the vasoconstrictor-mediated vasoconstriction except endothelin-1 in a concentration-dependent manner. CONCLUSIONS: The results suggested that in human IMA, AJ-2615 has an inhibitory effect on vasoconstriction mediated by a variety of vasoconstrictors and the mechanism of relaxation may be related to its calcium antagonism and alpha1-adrenergic receptor blocking activity. AJ-2615 may have important clinical implications for patients undergoing coronary artery bypass surgery for reversing and preventing graft spasm.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Vascular endothelial growth factor-mediated endothelium-dependent relaxation is blunted in spontaneously hypertensive rats.

The vasodilatory effect of VEGF has not been characterized in the setting of hypertension. This study investigated the in vitro vasorelaxant effects of VEGF in organ chambers in the aorta of the adult (12-week-old) spontaneously hypertensive rats (SHR), young (4-week-old) SHR without hypertension, and age-matched Wistar-Kyoto (WKY) rats compared with acetylcholine (ACh). Cumulative concentration-relaxation curves were established for VEGF (approximately 10(-12)-10(-8.5) M) and ACh (approximately 10(-10)-10(-5) M) in U46619 (10(-8) M)-induced contraction. VEGF induced endothelium-dependent relaxation that was significantly reduced in the adult SHR compared with the age-matched WKY control (87.8 +/- 2.8 versus 61.4 +/- 8.6%, P = 0.01). These responses were significantly attenuated by pretreatment with N(omega)-nitro-L-arginine (L-NNA, 300 microM) alone (SHR: 25.1 +/- 1.9%; WKY: 21.0 +/- 2.6%; P = 0.01) or indomethacin (7 microM) + L-NNA (SHR: 30.2 +/- 2.1%; WKY: 35.0 +/- 2.9%; P = 0.01). Further addition of oxyhemoglobin (20 microM) abolished the residual relaxation and reduced the relaxation induced by nitroglycerin. ACh induced similar responses to VEGF. In contrast, pretreatment with indomethacin alone enhanced VEGF- or ACh-induced relaxations and the effect was greater in the adult SHR than in WKY rats. In contrast to the adult SHR versus WKY rats, there were no significant differences of VEGF- or ACh-induced relaxations between young SHR and WKY rats. The results demonstrate that VEGF induces endothelium- or nitric oxide-dependent relaxation, which is blunted in the adult SHR. The mechanism of this impairment may be related to decreased release of NO although increased release of contracting factors from the dysfunctional endothelium may also be involved.

Acetylcholine↗
PubMed2001

Antinociceptive effect of astragalosides and its mechanism of action.

AIM: To study the effect and mechanism of astragalosides (AST) related to the antinociceptive activity. METHODS: The standardized formalin test was performed to induce the direct stimulation of nociceptors followed by inflammatory process in the Kunming strain mice. The involvement of opioid and nitric oxide was studied by subcutaneous injection of morphine with/without naloxone 30 min before formalin test, or peritoneal injection of L-arginine with/without L-NAME 20 min before formalin. RESULTS: AST 20, 40, and 80 mg/kg significantly lowered pain score of the second phase of formalin response as compared with control group (P<0.01). The maximum analgesic effect of AST 40 mg/kg was found at 4 h after the administration of AST (34.4 % inhibition at the second phase). Injection of morphine 5 mg/kg significantly inhibited pain response of both phases (P<0.01) and this was reversed by naloxone 2 mg/kg (P<0.01). However, naloxone did not alter the effect of AST on the second phase. Antinociceptive effect of AST 40 mg/kg was partially blocked by L-arginine 400 or 800 mg/kg (P<0.01). CONCLUSION: AST has an antinociceptive effect on formalin test in mice that is not mediated by the endogenous opioid system but related to its inhibitory effect on the production of NO.

Analgesics, Non-Narcotic↗
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

Effects of biatrial pacing in prevention of postoperative atrial fibrillation after coronary artery bypass surgery.

BACKGROUND: Atrial fibrillation (AF) is common after coronary artery bypass surgery (CABG) and results in prolonged hospitalization. The purpose of this study was to evaluate the efficacy of biatrial pacing in preventing post-CABG AF compared with single-site atrial pacing. METHODS AND RESULTS: A total of 132 patients who had no history of AF and who underwent CABG were randomized to 1 of the following 4 groups: biatrial pacing (BiA), left atrial pacing (LA), right atrial pacing (RA), or no pacing (control) in postoperative period. Overdrive atrial pacing was performed for 5 days. The incidence of AF was significantly reduced in the BiA group (12.5%) compared with the other 3 groups (LA, 36.4%; RA, 33.3%; control, 41. 9%; P<0.05). The mean length of hospital stay was significantly reduced in the BiA group. At baseline, the mean P-wave duration (P(dur)) and dispersion (P(dis)) were not prolonged. BiA pacing resulted in the most significant percentage of reduction in P(dis) when compared with the LA or RA groups (BiA, 42+/-8%; LA, 13+/-6%; RA, 10+/-9%; P<0.05 for BiA versus LA or RA). No significant differences existed in mean P(dur) and P(dis) between patients who developed AF and those who remained in sinus rhythm at baseline. However, only those patients who remained in sinus rhythm had a significant reduction in mean P(dur) and P(dis) after pacing therapy. CONCLUSIONS: Biatrial overdrive pacing is more effective in preventing post-CABG AF than single-site atrial pacing; this therapy also results in a shortened hospital stay. The overall reduction in atrial activation time with BiA pacing was reflected in the reduction in P(dis).

Aged↗
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

Inhibition of vasoconstriction by angiotensin receptor antagonist GR117289C in arterial grafts.

BACKGROUND: Angiotensin II (AII) has been suggested to be one of the important factors for genesis of graft spasm in coronary artery bypass surgery. The aim of this work was to investigate the effects of the nonpeptide angiotensin receptor AT1 antagonist GR117289C on the contraction induced by AII and other vasoconstrictors in isolated human internal mammary artery (IMA) preparations. METHODS: Two hundred eight IMA rings taken from 64 patients undergoing coronary artery bypass grafting were studied in organ baths. The interaction between GR117289C and AII or the other vasoconstrictors (U46619, norepinephrine, endothelin-1, and potassium chloride) was investigated in two ways. RESULTS: GR117289C induced near-maximal relaxation (94.5% +/- 2.9%) in IMA rings precontracted by AII. In IMA rings incubated with 1 or 10 nmol/L GR117289C, contractile responses to AII were attenuated in a concentration-related manner, whereas the dose-response curve did not shift to the right when higher doses of AII were administered, suggesting that the AT1 receptor blockade was noncompetitive in nature. Moreover, GR117289C also induced significant relaxation (82.9% +/- 8.1%) in IMA rings precontracted by U46619, but no inhibitory responses to U46619 could be observed when IMA rings were incubated with GR117289C. GR117289C did not alter responses to potassium chloride, norepinephrine, and endothelin-1. CONCLUSIONS: These results indicate that GR117289C is a potent, selective, noncompetitive AT1 receptor antagonist that may have a possible antagonistic effect on the thromboxane A2 receptor. Because AII and thromboxane A2 are important vasoconstrictors in the genesis of graft spasm, GR117289C may become an alternative treatment to relieve graft spasm.

Aged↗
PubMed2000

Injection of vasodilators into arterial grafts through cardiac catheter to relieve spasm.

Both native coronary artery and coronary bypass grafts may develop vasospasm after coronary artery bypass grafting. We recommend that whenever there is a high suspicion of vasospasm in arterial grafts and the native coronary artery unresponsive to or not suitable for usual vasodilator therapy, prompt selective graft arteriogram should be performed. Intraluminal injection of vasodilators such as calcium antagonists in combination with nitroglycerin may provide an effective antispastic therapy and this procedure could be lifesaving as demonstrated in the present report.

Aged↗
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

Vasorelaxant effect of phosphodiesterase-inhibitor milrinone in the human radial artery used as coronary bypass graft.

OBJECTIVE: The radial artery is a spastic coronary bypass graft. We investigated the effect of the phosphodiesterase III inhibitor milrinone on the human radial artery. METHODS: Radial artery segments (n = 76) taken from 15 patients were studied in an organ chamber. Concentration-relaxation curves for milrinone were established in the radial artery precontracted with 3 vasoconstrictors (phenylephrine, K(+), and U46619). In radial artery rings incubated with therapeutic plasma concentrations of milrinone (7 and 70 micromol/L) for 10 minutes, concentration-contraction curves for the 3 vasoconstrictors were constructed. RESULTS: Milrinone caused a submaximal relaxation in phenylephrine- (98.6% +/- 1.4%), K(+)- (89.1 +/- 4.5%), or U46619- (74.2 +/- 8.0%) precontracted radial arteries at -4.5 log(10) M. The EC(50) was higher against K(+) (-5.85 +/- 0.24 log(10) M, P =.02) or U46619 (-5. 21 +/- 0.61 log(10) M, P =.03) than phenylephrine (-6.68 +/- 0.11 log(10) M). Pretreatment with milrinone depressed the contraction by phenylephrine from 70.0% +/- 7.9% to 23.5% +/- 9.3% (P =.003) and by K(+) from 138.6% +/- 5.8% to 73.0% +/- 13.9% (P =.006) and shifted the EC(50) 3.8-fold higher (P =.03) for phenylephrine and 2.2-fold higher for K(+) (P =.01). Milrinone reduced the U46619 contraction at low concentration (-8.5 log(10) M) but had little effect on the maximal contraction. CONCLUSION: Milrinone is a potent vasodilator for the radial artery, with possibly higher potency in alpha-adrenoceptor- and depolarizing agent K(+)-mediated, but less potency in thromboxane A(2)-mediated, contraction. Because it also has a positive inotropic effect, this vasodilator may be particularly indicated for use in patients receiving radial artery grafts in coronary artery bypass grafting.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Comparative study on calcium channel antagonists in the human radial artery: clinical implications.

OBJECTIVES: The radial artery is spastic, and calcium channel antagonists have been used clinically in the radial artery for their antispastic effects. To choose a proper calcium channel antagonist for such a purpose, we compared the in vitro antispastic effects of 4 clinically used calcium channel antagonists (nicardipine, nifedipine, verapamil, and diltiazem) in the human radial artery. METHODS: Radial artery segments taken from patients undergoing coronary bypass operations were studied in the organ bath. The relaxation by the calcium channel antagonists was compared in the potassium-precontracted (25 mmol/L) radial artery. The inhibitory effect of the calcium channel antagonists at the clinically relevant plasma concentration and a higher concentration was also studied for the calcium channel antagonists. RESULTS: All calcium channel antagonists induced a full relaxation (97.8%-100%, n = 5-7 for each), with higher sensitivity (P =.005, analysis of variance [ANOVA] among the calcium channel antagonists for the effective concentration of the constrictor [or dilator] agent that caused 50% of maximal contraction [or relaxation]) to nifedipine (-7.37 +/- 0. 20 log(10) M) than nicardipine (-6.43 +/- 0.39 log(10) M, P =.1), verapamil (-6.08 +/- 0.13 log(10) M, P =.03), and diltiazem (-5.87 +/- 0.07 log(10) M, P =.01). Pretreatment with the plasma concentration of the calcium channel antagonists (60 nmol/L for diltiazem and 20 nmol/L for the others) inhibited the potassium-induced contraction (n = 6 for each) by nicardipine (from 138.6% +/- 5.8% to 101.4% +/- 7.6%, P =.001) and nifedipine (to 87. 7% +/- 6.8%, P =.0003) but not by verapamil (to 140.3% +/- 15.2%, P =.9) or diltiazem (to 132.8% +/- 7.3%, P =.8), although at higher contractions (-4.5 log(10) M) all 4 calcium channel antagonists abolished the contraction. CONCLUSIONS: Although all calcium channel antagonists have antispastic effects in the radial artery, the vessel has different sensitivities to them. Dihydropyridine derivatives may be the most potent calcium channel antiagonists and therefore are recommended for the clinical use for this purpose.

Analysis of Variance↗