UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Locally produced eicosanoids and endothelium-derived factors are believed to be the mediators of vascular tone of various vascular beds including the mesentery. Using a small vessel isometric myograph which allows direct measurement of microvascular reactivity, the interaction of eicosanoids and endothelium-derived relaxing factor (EDRF) in regulating vascular tone of mesenteric microcirculation of the rat was characterized. The microvascular response to various vasoactive agents before and after inhibition of prostacyclin production with indomethacin (INDO, 5 microM) and inhibition of EDRF synthesis with N omega-nitro-L-arginine methyl ester (L-NAME, 50 microM) was compared. Analysis of dose-response curves for prostaglandin F2 alpha (PGF2 alpha), U46619, a stable thromboxane analog, and norepinephrine (NE) after pretreatment with INDO demonstrated that inhibition of endogenous eicosanoids significantly attenuated the vasoconstrictor response to PGF2 alpha and U46619 but not to NE. Inhibition of EDRF synthesis with L-NAME potentiated the vasoconstrictor response to PGF2 alpha, U46619, and NE. These results suggest that EDRF acts as the primary mediator of vasodilator tone in the mesenteric microcirculation rather than vasodilator cyclooxygenase products such as prostacyclin. It also appears that the vasoconstrictor action of PGF2 alpha and U46619 may be mediated by a release of an endogenous indomethacin-sensitive factor.
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PMID:The interaction between endothelium-derived relaxing factor (EDRF) and eicosanoids in the regulation of the mesenteric microcirculation. 786 77

At present, there is no information on endothelin-1 (ET-1)-mediated vascular effects in the human spleen. The objectives of this study were to investigate the in vitro vascular responses to ET-1 using pharmacologic probes (selective ET receptor agonists/antagonists) and to characterize the ET receptor population in the human spleen. Spleens (n = 6) were removed from patients for treatment of underlying disease. The organs were perfused with warmed (37 degrees C), oxygenated (95% O2/5% CO2) Krebs solution at constant flow, with continuous recording of splenic arterial perfusion pressure (SAPP). The increases in SAPP caused by injection of ET-1 (ETA/ETB agonist) were markedly reduced in the presence of the selective ETA antagonist FR-139317, whereas those induced by IRL-1620 (an ETB agonist) and norepinephrine (NE) were unchanged. The increases in SAPP induced by intra-arterial bolus injections of NE and ET-1 were significantly (p < 0.05) potentiated by indomethacin [INDO; a cyclo-oxygenase (COX) inhibitor] alone and the responses to both peptides (ET-1 and IRL-1620) were significantly (p < 0.05) potentiated by INDO and L-NAME [a nitric oxide (NO) synthase inhibitor] together. We conclude that ET-1 contributes to the regulation of vascular tone in human spleen through activation of both ETA and ETB receptors and that these responses are modulated by concomitant release of prostaglandins and NO.
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PMID:Characterization of endothelin receptors in isolated, perfused human spleen. 959 40

Endothelium-dependent hyperpolarization of vascular smooth muscle cells (VSMCs) plays a crucial role in regulating vascular tone, especially in resistance vessels. It has been proposed that metabolites of arachidonic acid (AA), formed by cytochrome P-450 monooxygenase (P450), are endothelium-derived hyperpolarizing factors (EDHFs). These metabolites have been reported to mediate dilation to endogenous vasoactive compounds, such as bradykinin and acetylcholine. However, it is not known whether these metabolites of AA contribute to dilation of human resistance vessels. This is important since it has been proposed that EDHF serves as a compensatory mechanism to maintain dilation in disease states. Therefore, we studied the effect of AA on vessel diameter and VSMC membrane potential in isolated human coronary microvessels. Arterioles (81+/-5 microm, n=70) were dissected from right atrial appendages at the time of cardiac surgery and cannulated at a distending pressure of 60 mm Hg and zero flow. Changes in internal diameter were recorded with videomicroscopy. Some vessels were impaled with glass microelectrodes to measure membrane potential of VSMCs while internal diameters were simultaneously recorded. After constriction (47+/-2%) with endothelin-1, AA (10(-10)to 10(-5)mol/L) induced substantial dilation of human coronary microvessels, which was abolished by removal of the endothelium. Treatment with 17-octadecynoic acid (17-ODYA, 10(-5) mol/L; a P450 inhibitor) attenuated maximal dilation to AA (49+/-9% versus 91+/-4% [control]; P<0.05 versus control), whereas indomethacin (INDO, 10(-5) mol/L; a cyclooxygenase inhibitor) and N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/L; a NO synthase inhibitor) were without effect. Both 17-ODYA and miconazole (10(-5) mol/L, a chemically distinct P450 inhibitor) further reduced the dilation to AA in the presence of INDO. The presence of 40 mmol/L KCl or charybdotoxin (10(-8) mol/L, a blocker of large-conductance Ca2+-activated K+ channels) impaired dilation to AA (19+/-9% [KCI] versus 76+/-5% [control] and 47+/-6% [charybdotoxin] versus 91+/-3% [control]; P<0.05 for both). After depolarization with endothelin-1 (-26+/-1 mV from -48+/-3 mV [before endothelin]), AA (10(-5)mol/L) in the presence of INDO and L-NAME induced hyperpolarization of VSMCs (-57+/-5 mV). In the presence of 17-ODYA together with INDO and L-NAME, endothelin produced similar depolarization (-26+/-2 mV from - 48+/- 3 mV), but hyperpolarization to AA was reduced (-33+/-2 mV; P<0.05 versus absence of 17-ODYA). AA metabolites formed primarily by P450 produce potent endothelium-dependent dilation of human coronary arterioles via opening of Ca2+-activated K+ channels and hyperpolarization of VSMCs. These findings support an important role for P450 metabolites in the regulation of human coronary arteriolar tone.
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PMID:Human coronary arteriolar dilation to arachidonic acid depends on cytochrome P-450 monooxygenase and Ca2+-activated K+ channels. 973 72

1. Small mesenteric arteries from pregnant rats demonstrated greater sensitivity (pEC50 : P<0.001) and maximum relaxation (P<0.01) to acetylcholine (ACh) than those of control non-pregnant animals. 2. Maximum relaxation, but not sensitivity, to ACh remained greater (P<0.01) in pregnant animals when evaluated in 25 mM KCl, which prevents relaxation dependent upon hyperpolarization. ACh induced relaxation in the presence of 25 mM KCl was completely inhibited in pregnant and non-pregnant groups by N(omega)-nitro L-arginine methyl ester (L-NAME, 100 microM), indomethacin (INDO, 10 microM) and oxadiazole quinoxalin (ODQ, 1 microM), suggesting pregnancy associated enhancement of dilator prostanoid and/or nitric oxide (NO) synthesis. 3. ACh induced relaxation in 5 mM KCI was only partially inhibited by a combination of N(omega)-nitro L-arginine methyl ester (L-NAME, 100 microM), indomethacin (INDO, 10 microM) and oxadiazole quinoxalin (ODQ, 1 microM). The residual relaxation, which was greater in arteries from pregnant rats (maximum relaxation: P<0.01), was prevented by 25 mM KCl, indicating pregnancy associated enhanced synthesis/ reduced degradation of a hyperpolarizing factor. Residual relaxation to ACh in 5 mM KCl was inhibited by the cytochrome P450 inhibitor, proadifen (1 microM) in the pregnant group (P<0.001). 4. Relaxation to spermine NONOate was similar in pregnant and non-pregnant groups and totally inhibited by ODQ (in the presence of L-NAME). 5. This study suggests that, in addition to enhanced endothelium dependent NO/dilator prostanoid synthesis, a hyperpolarizing factor may contribute to the vascular adaptation to pregnancy.
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PMID:Enhanced acetylcholine induced relaxation in small mesenteric arteries from pregnant rats: an important role for endothelium-derived hyperpolarizing factor (EDHF). 980 27

Oxygen free radicals (OFR) play a primary role in ischemia-reperfusion-mediated vascular dysfunction and this is paralleled by a loss of endothelial nitric oxide synthase (eNOS) activity. The authors tested whether a direct exposure to OFR may affect vascular relaxation by altering nitric oxide (NO) release. Effects of electrolysis(EL)-generated OFR on basal and agonist-evoked NO release were monitored in isolated rat hearts by oxyhemoglobin assay. Electrolysis-induced changes were compared with those obtained after 30 min perfusion with NOS and cyclooxygenase (COX) inhibitors NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) and indomethacin (INDO, 1 m M). Electrolysis-generated hydroxyl radical (.OH) formed by.O2-and H2O2 via the Fenton reaction as revealed by Electron Paramagnetic Resonance (EPR). After EL, basal NO release declined by 60% and coronary perfusion pressure (CPP) increased by approximately 70%. L-NAME/INDO perfusion similarly lowered NO release (-63%) but increased CPP less than EL (56+/-3%P<0.03 v post-EL). In presence of excess substrates and cofactors eNOS activity was not affected by EL. Both acetylcholine (ACh; 1 microM) and bradykinin (BK; 10 n M) had minimal effect in reversing EL-induced vasoconstriction, whereas both partially reversed L -NAME/INDO-mediated constriction. Sodium nitroprusside (SNP, 1 microM) completely reversed L-NAME/INDO constriction and partly countered that after EL (-38+/-2.5, P<0.001). Acetylcholine-evoked NO release was nearly abolished by both treatments whereas BK still elicited partial NO release after eNOS/cyclooxygenase inhibition (P<0.001) but not after EL. In conclusion, OFR severely impair NO-mediated coronary vasorelaxation affecting both basal and agonist-evoked NO release but not eNOS activity. However, EL also significantly blunts NOS/COX-independent vasodilation suggesting alteration of other vasodilatative pathways.
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PMID:Oxygen radical-mediated reduction in basal and agonist-evoked NO release in isolated rat heart. 1134 Dec 36

To determine the effects and mechanism(s) of genistein on endothelial functions, the model of mesenteric-chamber with intravital fluorescence videomicroscopy and image analysis were used. After preconstriction with norepinephrine (NE; 10(-6) M), vascular responses to different doses of genistein (10(-2)-10(-7) M) were recorded with real time video-camera. The mechanism(s) of vasodilation was also determined by using N(omega)-L-arginine methyl ester (L-NAME; 100 microM), the inhibitor of nitric oxide synthase (NOS inhibitor), and/or indomethacin (INDO; 10 microM), cyclooxygenase inhibitor. The results indicated that the topical application of 10(-2)-10(-7) M genistein on mesenteric microvessels caused the increase in arteriolar diameters from 33% to 48%, respectively. The effects of genistein on mesenteric endothelial-dependent vasodilatation could be mediated through both L-arginine/NO and cyclooxygenase pathways. Our finding indicated that genistein could induce endothelial-dependent vasodilation similar to 17beta-estradiol.
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PMID:The vascular effect of genistein: what is its mechanism, nitric oxide or PGI2? 1654 23

Limb differences in endothelial function exist between arm and leg vasculatures of humans. The current investigation tested the hypothesis that forelimb and hindlimb vasorelaxation are similar in the absence of limb differences in blood pressure. Conduit arteries (brachials/femorals) and second order arterioles were harvested from 22 miniature Yucatan swine. In vitro assessment of vasorelaxation was determined by administering increasing doses of bradykinin (BK), acetylcholine (ACh), and sodium nitroprusside (SNP). The role of the nitric oxide synthase (NOS) and cyclooxygenase (COX) pathways was assessed in conduit arteries but not resistance arterioles through L-NAME (300 microM) and INDO (5 microM) incubation, respectively. The relaxation responses to BK and ACh were similar in brachial and femoral arteries. SNP relaxation response was greater in the brachial compared to femoral arteries. There were also no significant differences in the relaxation responses of second order arterioles of the forelimb and hindlimb to BK, ACh, and SNP. Incubation of conduit arterial rings in L-NAME produced a greater reduction in BK and ACh relaxation in the brachial (approximately 25%) compared to femoral (approximately 13%) arterial rings. The current results of this investigation suggest that the forelimb and hindlimb vasculatures of swine have relatively similar vasorelaxation responses to both endothelium-dependent and -independent vasodilators.
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PMID:Endothelium-dependent and -independent relaxation in the forelimb and hindlimb vasculatures of swine. 1754 6

The vascular effects of an aqueous extract prepared from the leaves of Eucommia ulmoides Oliv. (ELE), a medicinal herb commonly used in antihypertensive herbal prescriptions in China, were investigated in rat mesenteric resistance arteries. The mesenteric vascular bed was perfused with Krebs solution and the perfusion pressure was measured with a pressure transducer. In preparations with an intact endothelium and precontracted with 7 microM methoxamine, perfusion of ELE (107102 mg/ml for 15 min) caused a concentration-dependent vasodilatation, which was abolished by chemical removal of the endothelium. The ELE-induced vasodilatation was inhibited by neither indomethacin (INDO, a cyclooxygenase inhibitor) nor NG-nitro-L-arginine-methyl ester (L-NAME, a nitric oxide inhibitor). The ELE-induced vasodilatation was significantly inhibited by tetraethylammonium (TEA, a K channel blocker) and 18alpha-glycyrrhetinic acid (18alpha-GA, a gap-junction inhibitor), and abolished by high K-containing Krebs' solution. Atropine (a muscarinic acetylcholine receptor antagonist) significantly inhibited the vasodilatation induced by ELE at high concentrations. These results suggest that the ELE-induced vasodilatation is endothelium-dependent but nitric oxide (NO)- and prostaglandin I2 (PGI2)-independent, and is mainly mediated by the endothelium-derived hyperpolarizing factor (EDHF) in the mesenteric resistance arteries. Furthermore, the ELE-induced EDHF-mediated response involves the activation of K-channels and gap junctions.
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PMID:Endothelium-derived hyperpolarizing factor (EDHF) mediates endothelium-dependent vasodilator effects of aqueous extracts from Eucommia ulmoides Oliv. leaves in rat mesenteric resistance arteries. 1898 92

Nitrosyl ruthenium complexes have been characterized as nitric oxide (NO) donors that induce relaxation in the denuded rat aorta. There are some differences in their vascular relaxation mechanisms compared with sodium nitroprusside. This study investigates whether the endothelium could interfere with the [Ru(terpy)(bdq)NO](3+)-TERPY-induced vascular relaxation, by analyzing the maximal relaxation (Emax) and potency (pD(2)) of TERPY. Vascular reactivity experiments showed that the endothelium negatively modulates (pD(2): 6.17+/-0.07) the TERPY relaxation in intact rat aortic rings compared with the denuded rat aorta (pD(2): 6.65+/-0.07). This effect is abolished by a non-selective NO-synthase (NOS) inhibitor L-NAME (pD(2): 6.46+/-0.10), by the superoxide anion (O(2)(-)) scavenger TIRON (pD(2): 6.49+/-0.08), and by an NOS cofactor BH(4) (pD(2): 6.80+/-0.10). The selective dye for O(2)(-) (DHE) shows that TERPY enhances O(2)(-) concentration in isolated endothelial cells (intensity of fluorescence (IF):11258.00+/-317.75) compared with the basal concentration (IF: 7760.67+/-381.50), and this enhancement is blocked by L-NAME (IF: 8892.33+/-1074.41). Similar results were observed in vascular smooth muscle cells (concentration of superoxide after TERPY: 2.63+/-0.17% and after TERPY+L-NAME: -4.63+/-0.14%). Considering that TERPY could induce uncoupling NOS, thus producing O(2)(-), we have also investigated the involvement of prostanoids in the negative modulation of the endothelium. The non-selective cyclooxygenase (COX) inhibitor indomethacin and the selective tromboxane (TXA(2)) receptor antagonist SQ29548 reduce the effect of the endothelium on TERPY relaxation (pD(2) INDO: 6.80+/-0.17 and SQ29548: 6.85+/-0.15, respectively). However, a selective prostaglandin F(2alpha) receptor antagonist (AH6809) does not change the endothelium effect. Moreover, TERPY enhances the concentration of TXA(2) stable metabolite (TXB(2)), but this effect is blocked by L-NAME and TIRON. The present findings indicate that TERPY induces uncoupling of eNOS, enhancing O(2)(-) concentration. This enhancement in O(2)(-) concentration induces COX activation, producing TXA(2), which negatively modulates the rat aorta relaxation induced by the NO donor TERPY.
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PMID:Endothelium negatively modulates the vascular relaxation induced by nitric oxide donor, due to uncoupling NO synthase. 1969 34

Endothelium-dependent vasodilation is mediated by nitric oxide (NO), prostaglandins (PG), and endothelium-derived hyperpolarizing factor (EDHF). We studied the contributions and temporal characteristics of these components in the renal vasodilator responses to acetylcholine (ACh) and bradykinin (BK) and in the buffering of vasoconstrictor responses to norepinephrine (NE) and angiotensin II (ANG II). Renal blood flow (RBF) and vascular conductance (RVC) were studied in anesthetized rats in response to renal arterial bolus injections before and after inhibition of NO-synthase (N(G)-nitro-L-arginine methyl ester, L-NAME), cyclooxygenase (indomethacin, INDO), or both. ACh increased RVC peaking at maximal time (tmax) = 29 s. L-NAME (n = 8) diminished the integrated response and made it substantially faster (tmax = 18 s). The point-by-point difference caused by L-NAME (= NO component) integrated to 74% of control and was much slower (tmax = 38 s). INDO (n = 9) reduced the response without affecting tmax (36 vs. 30 s). The difference (= PG) reached 21% of the control with tmax = 25 s. L-NAME+INDO (n = 17) reduced the response to 18% and markedly accelerated tmax to 16s (= EDHF). Results were similar for BK with slightly more PG and less NO contribution than for ACh. Constrictor responses to NE and ANG II were augmented and decelerated by L-NAME and L-NAME+INDO. The calculated difference (= buffering by NO or NO+PG) was slower than the constriction. It is concluded that NO, PG, and EDHF contribute >50%, 20-40%, and <20% to the renal vasodilator effect of ACh and BK, respectively. EDHF acts substantially faster and less sustained (tmax = 16 s) than NO and PG (tmax = 30 s). Constrictor buffering by NO and PG is not constant over time, but renders the constriction less sustained.
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PMID:Temporal characteristics of nitric oxide-, prostaglandin-, and EDHF-mediated components of endothelium-dependent vasodilation in the kidney. 2398 61

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