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At least 811 records · Page 45Linked to original sources
PubMed1999

Inhibition of endothelium-dependent relaxation by Candida albicans.

This study examines the effects of Candida albicans on acethylcholine-induced, endothelium-dependent relaxation of thoracic aorta of rabbits, precontracted by phenylephrine (10(-7) M). Isolated vessel rings were incubated with C. albicans, Saccharomyces cerevisiae, or their mannans, and endothelium-dependent relaxation was measured by the induction of acethylcholine. Endothelium-dependent relaxation remained unaffected after 3 hours by either C. albicans or S. cerevisiae, or their mannans. After 24 hours, however, incubation with C. albicans had completely abolished relaxation, whereas relaxation was decreased by mannan of C. albicans and continued unaffected by S. cerevisiae. In contrast, no change was registered with a 24 hours incubation of C. Albicans in a sodium nitroprusside-induced, endothelium-independent, vascular smooth muscle relaxation. Microscopical investigation of the morphological structure of vessel walls revealed penetration of C. albicans on the intimal surface after 3 hours incubation and infiltration of the yeast through the vessel wall after 24 hours. No changes in vessel morphology occurred after 3 or 24 hours with S. cerevisiae or the mannan of C. albicans. These results show the ability of C. albicans to inhibit endothelium-dependent, but not endothelium-independent, relaxation of vascular smooth muscle and may have important implications for functional damage to endothelial cells and the regulation of vessel tone and blood flow.

Acetylcholine↗
PubMedDate not supplied

Vascular endothelium: vasoactive mediators.

In most blood vessels, the endothelium generates both vasodilator and growth-stabilizing mediators under normal physiological circumstances. The vasodilator influence of the endothelium modulates the vasoconstriction induced by adrenergic nerves, bloodborne substances, and local autacoids. Nitric oxide (NO) is a major endothelium-derived vasodilator, along with prostacyclin. A third substance called endothelium-derived hyperpolarizing factors (EDHF) mediates vasodilatation in certain conduit arteries and in most resistance vessels. EDHF may be a cytochrome P-450 metabolite of arachidonic acid. NO acts mostly through an elevation of cyclic guanosine monophosphate in vascular smooth muscle, whereas prostacyclin stimulates adenylate cyclase. The mode of action of EDHF involves the activation of K+ channels. The multiplicity of the factors released by the endothelium, as well as the complexity of the interactions among these factors and those with other nonendothelial mediators, determine the extent of vasomotor control exerted locally by the endothelium.

Animals↗
PubMed1997

Botulinolysin, a thiol-activated hemolysin produced by Clostridium botulinum, inhibits endothelium-dependent relaxation of rat aortic ring.

The effects of botulinolysin (Blyn), a thiol-activated hemolysin produced by Clostridium botulinum, on contractility of rat aortic ring were studied in order to clarify an underlying mechanism of vasoconstriction by the toxin observed previously as an increase in perfusion pressure in isolated rat organs. Blyn (30 hemolytic units/ml; HU/ml) itself did not elicit any apparent change in resting tension of the ring. Contractile tension elicited by a high concentration of phenylephrine in endothelium-intact rings increased significantly after treatment with Blyn (30 HU/ml), while phenylephrine-induced contraction of endothelium-denuded rings was not influenced by toxin treatment. In rings with intact endothelium, acetylcholine (ACh)-induced relaxation was significantly inhibited after treatment with Blyn (30, 10, 1 HU/ml). In contrast, relaxation of denuded rings by sodium nitroprusside was not affected by toxin treatment (30 HU/ml). Arginine (10(-4) M) partly reversed the inhibition of ACh-induced relaxation by the toxin (1 HU/ml). Endothelium-dependent relaxation by histamine or adenosine triphosphate was also inhibited by Blyn (1 HU/ml), but the relaxation elicited by calcium ionophore A23187 was not influenced by the toxin. The results indicate that Blyn acts on endothelium and inhibits agonist-induced endothelium-dependent relaxation of blood vessels.

Acetylcholine↗
PubMed1999

On the control of the plasma contact activation system on human endothelium: comparisons with heparin surface.

The endothelial lining in segments of the human saphenous vein harvested before and shortly after systemic heparinization of patients was investigated with regard to the ability to inhibit activated FXII. Comparisons were made with a surface modified by endpoint attached heparin, which, like the endothelium, is negatively charged and exposes the specific antithrombin binding sequence and also binds FXII and antithrombin. The heparin surface preincubated with plasma or blood and endothelium in vivo having been exposed to non-heparinzed blood and expressed similar amounts of FXII but no FXIIa. On both surfaces activation of bound FXII with ellagic acid resulted in consumption of the proenzyme and in inhibition of formed FXIIa. On both heparin surface and the endothelium consumption of antithrombin occurred concomitantly, demonstrating the importance of this inhibitor in the control of contact activation system. On the endothelium, in vivo or ex vivo, exposed to heparinized blood, most FXII was present in the active form and only incubation with purified antithrombin could restore the FXIIa inhibitory capacity. It is suggested that antithrombin bound by the specific antithrombin binding sequence of endothelial heparan sulphate, like antithrombin bound to the specific antithrombin binding sequence on heparin surface, inhibits alpha-FXIIa. This makes the endothelium consonant with the plasma contact activation system. It is suggested that systemic heparinzation of patients may both activate endothelial bound FXII and interfere in the inhibition of formed FXIIa by depriving the endothelium of required amounts of antithrombin.

Anticoagulants↗
PubMed2000

Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells.

BACKGROUND: Vascular endothelial cells lost from the blood-vessel endothelium through necrosis or apoptosis must be replaced. We investigated in a leukaemia model whether bone-marrow-derived endothelial cells contribute to this maintenance angiogenesis. METHODS: We studied six patients with chronic myelogenous leukaemia (CML) carrying the BCR/ABL fusion gene in their bone-marrow-derived cells. We screened endothelial cells generated in vitro from bone-marrow-derived progenitor cells and vascular endothelium in myocardial tissue for the BCR/ABL fusion gene by in-situ hybridisation. For detection of donor-type endothelial cells after transplantation of haemopoietic stem cells, recipient tissue was stained with monoclonal antibodies against donor-type HLA antigens. FINDINGS: We identified the BCR/ABL fusion gene in variable proportions (0-56%) of endothelial cells generated in vitro. Endothelial cells expressing the fusion gene were found in the vascular endothelium of a patient. In a recipient of an allogeneic stem-cell transplant, normal donor-type endothelial cells were detected in the vascular endothelium. INTERPRETATION: These findings suggest that CML is not solely a haematological disease but originates from a bone-marrow-derived haemangioblastic precursor cell that can give rise to both blood cells and endothelial cells. Moreover, normal bone-marrow-derived endothelial cells can contribute to the maintenance of the blood vascular endothelium. The integration of bone-marrow-derived endothelial cells into the vascular endothelium provides a rationale for developing vascular targeting strategies in vasculopathies, inflammatory diseases, and cancer.

Adult↗
PubMed1981

Peripheral recipient endothelium following corneal transplantation.

The central graft endothelium and peripheral recipient endothelium of 16 corneas of 14 patients following corneal transplantation were studied using the technique of specular microscopy. There was a wide discrepancy in the morphologic profile between the endothelium from these two regions of the cornea, suggesting that both donor and recipient endothelium maintain their morphologic autonomy following corneal transplantation. There was evidence that graft endothelium may be more active participant in the healing process at the graft-recipient junction than the recipient endothelium.

Adolescent↗
PubMed2000

Endothelium-dependent vasorelaxant and antiproliferative effects of apigenin.

This study was designed to determine whether the relaxant effect of apigenin was endothelium dependent and to examine the possible antiproliferative effect of apigenin. Apigenin relaxed the phenylephrine-precontracted endothelium-intact aortic rings with IC(50) value of 3.7+/-0.5 microM and removal of a functional endothelium significantly attenuated this relaxation (IC(50)=8.2+/-0.9 microM). However, apigenin did not affect the 0.1 microM phorbol 12,13-dibutyrate-induced contraction (IC(50)=34.6+/-1.2 microM) within the concentration range that relaxed the phenylephrine-contracted arteries, suggesting that apigenin did not influence protein kinase C-mediated contractile mechanisms in rat aorta. Pretreatment of apigenin significantly potentiated the relaxant effect of acetylcholine on phenylephrine-induced contraction. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) or methylene blue reduced the relaxant effect of apigenin. Apigenin (10 microM) increased the guanosine 3',5'-cyclic monophosphate (cGMP) content of endothelium-intact tissues. Pretreatment with L-NAME (100 microM) or removal of endothelium significantly suppressed the effect of apigenin on cGMP production. In addition, apigenin significantly inhibited [3H]thymidine incorporation into DNA of primary cultured rat aortic smooth muscle cell in a dose-dependent manner. These findings suggest that besides influx and release of Ca(2+), nitric oxide (NO) and cGMP may account for the apigenin-induced endothelium-dependent relaxation and hypotensive activity. Both vasorelaxant and antiproliferative activities may contribute to a benefit of apigenin in the vascular system.

Animals↗
PubMed2000

Nitric oxide-mediated endothelium-dependent relaxation of rat thoracic aorta induced by aqueous extract of red rice fermented with Monascus ruber.

Vasodilatory effects of aqueous extract of red rice fermented with Monascus ruber IFO32318 were examined on the isolated rat aorta. The water phase of fermented rice with Monascus (WP/FRM, 0.1-10 mg/ml) caused a transient relaxation of the endothelium-intact rat aorta precontracted with norepinephrine (NE, 300 nM). The WP/FRM-induced relaxation was abolished by removal of endothelium or in the presence of N(G)-nitro-L-arginine (L-NNA, 10 microM), a nitric oxide (NO) synthase inhibitor. Neither atropine, a muscarinic receptor antagonist (10 microM), nor indomethacin, a cyclooxygenase inhibitor (10 microM), altered the WP/FRM-induced endothelium-dependent relaxation. gamma-Aminobutyric acid (GABA), one of the principle components of the extract, did not affect the muscle tension of the aorta with intact endothelium. In addition, WP/FRM increased the production of NO in primary cultured endothelial cells from human umbilical vein. The enhanced production of NO by WP/FRM was diminished by pretreatment with L-NNA (10 microM). In conclusion, WP/FRM induces relaxation of rat aorta by releasing NO from endothelium. There seem to be some unknown factor(s) other than acetylcholine (Ach) and GABA, in the aqueous extract of red rice, which stimulate vascular endothelial cells to produce and/or release NO leading to endothelium-dependent relaxation by WP/FRM.

Acetylcholine↗
PubMed2001

Radiation therapy impairs endothelium-dependent vasodilation in humans.

OBJECTIVES: The objective of this study was to test the hypothesis that external-beam radiation induces a chronic impairment of endothelium-dependent vasodilation. BACKGROUND: Radiation therapy is used commonly in the treatment of cancer and is associated with an increased incidence of adverse vascular events related to the field of radiation, including stroke and myocardial infarction. As endothelial injury is central to the pathogenesis of vascular diseases, we hypothesized that radiotherapy induces arterial endothelial dysfunction. METHODS: Sixteen women with unilateral breast cancer who underwent standard external-beam radiation therapy to the breast and axilla >3 years before enrollment and ten healthy women were studied. Vascular ultrasonography was used to image both the artery exposed to radiation and the contralateral artery. Flow-mediated, endothelium-dependent vasodilation and endothelium-independent vasodilation to nitroglycerin of both axillary arteries were measured. RESULTS: Endothelium-dependent vasodilation was significantly impaired in the irradiated axillary arteries compared with the contralateral, nonirradiated arteries (-0.4 +/- 0.4% vs. 3.2 +/- 0.8% p < 0.001) and also compared with control subjects' arteries (-0.4 +/- 0.4% vs. 2.5 +/- 0.6%, p < 0.001). In contrast, endothelium-independent vasodilation was greater in the arteries that received radiation compared with the contralateral arteries (3.8 +/- 0.5% vs. 2.0 +/- 0.4%, p < 0.05) and also compared with control arteries (3.8 +/- 0.5% vs. 2.5 +/- 0.4%, p < 0.05). CONCLUSIONS: External beam radiation therapy impairs endothelium-dependent vasodilation of conduit arteries, implicating a decrease in the bioavailability of nitric oxide. These abnormalities may contribute to the development of arterial occlusive disease and associated clinical events.

Aged↗
PubMedDate not supplied

Pregnancy induces expression of cPLA2 in ovine uterine artery but not systemic artery endothelium.

OBJECTIVE: To determine whether pregnancy increases cytosolic phospholipase A2 (cPLA2) expression in uterine artery (UA) endothelial cells and vascular smooth-muscle (VSM) cells, and whether ovarian steroids mediate this effect. METHODS: Uterine arteries and omental arteries (systemic control) were isolated from pregnant (120-130 days' gestation) ewes and from nonpregnant ewes synchronized to the corresponding phases of the ovarian cycle (follicular or luteal) or ovariectomized. In addition, ovariectomized ewes were treated with vehicle, estradiol-17 beta (E2 beta), progesterone (P4), or combined E2 beta/P4 for 10 days, and UAs were collected. Arteries from all studies were separated into mechanically isolated endothelial and VSM fractions. Proteins were then solubilized and separated on 7.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western immunoblotting using an affinity-purified mouse monoclonal antibody for cPLA2. RESULTS: Both UA endothelium and VSM fractions were seen to express cPLA2, detected as a single band with a molecular mass similar to that observed in myometrium (about 100 kD). Distribution of cPLA2, when expressed per microgram of protein, was observed as 40% in UA endothelium compared with 60% in VSM fractions. Uterine artery endothelial cPLA2 expression was specifically increased 1.9-fold in pregnancy (P < .05), whereas there was no significant change from VSM. Furthermore, in ovariectomized sheep versus intact luteal or follicular phase animals, there was no significant change in cPLA2 expression in endothelium or VSM. Administration of E2 beta, P4, or their combination in ovariectomized sheep also failed to reproduce the pregnancy-induced increase in cPLA2 expression in UA endothelium. Omental artery endothelial and VSM cPLA2 expression was observed at similar magnitudes as UA expression, but levels were consistently unchanged by pregnancy, the ovarian cycle, or ovariectomy. CONCLUSIONS: cPLA2 was expressed throughout the endothelium and VSM of both uterine and omental arteries, but only in UA endothelium was pregnancy associated with elevated cPLA2 expression. The lack of change in cPLA2 expression with the ovarian cycle or in ovariectomized animals, even after prolonged treatment with E2 beta, P4, or E2 beta/P4 combined suggests this pregnancy-induced increase in cPLA2 may not be estrogen and/or progesterone dependent.

Animals↗
PubMed1996

Role of endothelium in control of forearm blood flow in patients with heart failure.

We studied the role of endothelium in control of forearm blood flow during reactive and exercise hyperemia in patients with heart failure as well as in normal subjects. First, endothelium-dependent forearm vasodilation in response to acetylcholine (ACh), substance P, and endothelium-independent forearm vasodilation in response to sodium nitroprusside (SNP) were examined in patients with heart failure and in normal subjects. Endothelium-dependent forearm vasodilation in response to ACh but not to substance P was impaired in patients with heart failure. Endothelium-independent forearm vasodilation to SNP was also preserved in patients with heart failure. Second, the role of nitric oxide (NO) in reactive hyperemia and exercise hyperemia was examined in normal subjects using NG-monomethyl-L-arginine (L-NMMA), a blocker of NO synthesis. Results suggest that NO plays a minimal role in peak reactive hyperemia and exercise hyperemia in normal human forearm vessels. Finally, we determined if L-arginine, a precursor of NO, improves impaired endothelium-dependent vasodilation due to ACh and reactive and exercise hyperemia in patients with heart failure. L-Arginine augmented impaired ACh-induced vasodilation as well as reactive and exercise hyperemia in patients with heart failure. Our results suggest that defective endothelial function may contribute to abnormal control of forearm blood flow in patients with heart failure.

Acetylcholine↗
PubMed1997

Acceleration of impairment of endothelium-dependent responses under poor runoff conditions in canine autogenous vein grafts.

OBJECTIVES: To assess the effects of changes in shear stress on endothelium-dependent responses. MATERIALS AND METHODS: Autologous vein grafts were implanted in poor or normal distal runoff limbs of 10 mongrel dogs. Six weeks after grafting the vein grafts were removed, cut into rings, and suspended in organ chambers for isometric tension recording. RESULTS: The average value of intimal thickening was 110.7 +/- 45.2 microns in poor runoff limbs and 65.5 +/- 27.9 microns in control limbs, respectively. There was a significant difference between the two groups. Acetylcholine caused comparable endothelium-independent contractions in both groups. In the control group, adenosine diphosphate, thrombin and A23187 caused endothelium-dependent relaxations. In the poor runoff group, the endothelium-dependent relaxations caused by adenosine diphosphate and thrombin were impaired, while A23187 caused comparable endothelium-dependent relaxations. Direct relaxations in response to sodium nitroprusside were comparable between the two groups. CONCLUSIONS: This dysfunction of the endothelium under conditions of abnormal flow may accelerate intimal thickening of the vein graft and result in late graft failure.

Animals↗
PubMed2003

Endothelium and smooth muscle of pig coronary artery: differences in metabolism.

Here, we report that the smooth muscle and endothelium of the pig coronary artery differ in the profiles of energy metabolism nucleotides. ATP levels in the freshly isolated smooth muscle (1490 +/- 93, all the values are in pmol/mg protein) were significantly greater than in the endothelium (418 +/- 68). In contrast, endothelium contained higher levels of NADH (328 +/- 21), NAD+ (1210 -/+ 28), NADPH (87 +/- 2), and NADP+ (77 +/- 4) than smooth muscle (17 +/- 2, 96 +/- 14, 7 +/- 1, and 8 +/- 1, respectively). However, smooth muscle and endothelium do not differ from each other in the ratios of NADH/NAD+ or NADPH/NADP+. Cells cultured from smooth muscle and endothelium contained less ATP (93 +/- 2, 141 +/- 6) and had lower ratios of NADH/ NAD+ than the freshly isolated tissues but the NADPH/NADP+ ratios remained similar. We conclude that (a) freshly isolated smooth muscle and endothelium differ in their profiles of the energy metabolism nucleotides, and (b) culturing the cells alters the profile.

Adenosine Triphosphate↗
PubMedDate not supplied

Endothelium-dependent relaxation in rat aorta may be mediated through cyclic GMP-dependent protein phosphorylation.

The action of some vascular smooth muscle relaxants depends on the presence of the endothelium. We have recently shown that relaxation may be mediated through the formation of cyclic GMP. The nitrovasodilators are another class of relaxants which exert their effects through the formation of cyclic GMP, although their relaxation is independent of the presence of the endothelium. Their relaxant properties seem to depend on free radical formation--specifically, the formation of nitric oxide. The NO-induced smooth muscle relaxation is proposed to occur through activation of guanylate cyclase and the formation of cyclic GMP. Protein phosphorylation is thought to be a common event in the pathway for many biological phenomena. Moreover, sodium nitroprusside and 8-bromo cyclic GMP induce similar patterns of protein phosphorylation in intact rat thoracic aorta. Here we report that the patterns of protein phosphorylation induced by the endothelium-dependent vasodilators and nitrovasodilators were identical. Incorporation of 32P into myosin light chain was decreased by both classes of agents. Removal of the endothelium abolished the changes in phosphorylation with the endothelium-dependent vasodilator (acetylcholine), but not those with the nitrovasodilator (sodium nitroprusside). These results suggest that endothelium-dependent vasodilators and nitrovasodilators induce relaxation through cyclic GMP-dependent protein phosphorylation and dephosphorylation of myosin light chain.

Acetylcholine↗
PubMed1997

Endothelium-dependent relaxation by substance P in human isolated omental arteries and veins: relative contribution of prostanoids, nitric oxide and hyperpolarization.

1. The objective of the present study was to investigate human omental arteries and veins with respect to: (i) the contractile effect of the thromboxane A2 analogue U46619, (ii) endothelium-dependency and mediators of the relaxing effect of substance P (SP) and acetylcholine (ACh). 2. Changes in isometric tension in response to administration of U46619, SP and ACh were measured in human isolated omental arteries and veins with and without endothelium. To investigate the mechanism of action of SP, the SP-induced relaxation was measured in the presence of indomethacin (cyclo-oxygenase inhibitor), NG-monomethyl-L-arginine (L-NMMA, nitric oxide-synthase inhibitor), KCl (inhibitor of endothelium-dependent hyperpolarization), tetraethylammonium (TEA; non-selective inhibitor of K(+)-channels, with some preference for the high conductance Ca(2+)-activated K(+)-channel, BKCa), glibenclamide (inhibitor of the ATP-sensitive K(+)-channel) and/or clotrimazole (inhibitor of the cytochrome P450-system and the intermediate conductance Ca(2+)-activated K(+)-channel, IKCa). 3. U46619 contracted both the artery and the vein segments. Endothelium removal did not alter the contraction. 4. ACh caused neither contraction nor relaxation in artery and vein segments precontracted with U46619. 5. In both artery and vein segments precontracted with U46619, SP produced endothelium-dependent relaxation. The relaxation was unaffected by indomethacin, but was incompletely reduced by L-NMMA and KCl respectively. The L-NMMA-resistent relaxation was abolished in the presence of KCl. 6. TEA inhibited the SP-induced relaxation in artery and vein segments both in the presence and absence of L-NMMA and indomethacin, while glibenclamide and clotrimazole had no effect. 7. In conclusion, the SP-induced relaxation in human omental arteries and veins seems to be mediated via NO and endothelium-dependent hyperpolarization. KATP and IKCa are probably not involved in the hyperpolarization, but activation of BKCa may contribute to the hyperpolarization. Prostanoid synthesis and the cytochrome P450-system are probably not involved in the SP-induced relaxation in this area.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Endothelium-independent relaxation of aortic rings by the nitric oxide synthase inhibitor diphenyleneiodonium.

1. The flavoprotein binder diphenyleneiodonium (DPI) is a potent, irreversible inhibitor of nitric oxide synthase (NOS), but produces only a transient pressor response following systemic administration to animals, despite evidence of persistent NOS inhibition. To characterize further the effects of DPI on vascular tone, isometric tension was recorded from rat isolated aortic rings mounted between steel wires in an organ bath. 2. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 1 mM) initiated an additional contraction of prostaglandin F2 alpha-preconstricted rings with endothelium which was sustained throughout the period of L-NAME exposure (+234 +/- 39% at 15 min). In contrast, addition of DPI (5 microM) to rings with endothelium produced a transient initial contraction (+111 +/- 27% at 2 min) followed by a more sustained relaxation (-27 +/- 19% at 15 min, P < 0.001 vs L-NAME). 3. The contraction to DPI was also observed in rings without endothelium, was abolished by L-NAME pretreatment, and was unaffected by the alpha-adrenoreceptor inhibitor prazosin. Relaxation in response to DPI was not inhibited by endothelium removal or by pretreatment with either L-NAME or with the ATP-sensitive potassium channel blocker glibenclamide. 4. The endothelium-independent relaxation to DPI was inhibited at 23 degrees C and its time course was delayed by pretreatment with the guanylate cyclase inhibitor methylene blue. 5. Thus, in addition to a transient initial contraction due to NOS inhibition, DPI produces an endothelium-independent, temperature-dependent relaxation which appears in part due to activation of guanylate cyclase. This relaxant effect of DPI may explain the transient nature of its pressor effect in vivo despite sustained NOS inhibition.

Adrenergic alpha-Antagonists↗
PubMed1997

Role of endothelium and nitric oxide in histamine-induced responses in human cranial arteries and detection of mRNA encoding H1- and H2-receptors by RT-PCR.

1. Histamine induces relaxation of human cranial arteries. Studies have revealed that the relaxant histamine H1-receptor predominates in human cerebral and the H2-receptor in temporal arteries, while H1- and H2-receptors are of equal importance in the middle meningeal artery. The purpose of the present study was to examine the role of the endothelium and nitric oxide in histamine-induced responses and to show the presence of mRNA encoding H1- and H2-receptors in human cranial arteries. 2. Electrophoresis of polymerase chain reaction (PCR) products from human cerebral, middle meningeal and temporal arteries, demonstrated products corresponding to mRNA encoding both H1- and H2-receptors in arteries with and without endothelium. The amplified PCR products were sequenced and showed 100% homology with the published sequences of these histamine receptors. 3. A sensitive in vitro system was used to study vasomotor responses to histamine. In precontracted cerebral, middle meningeal and temporal arteries with and without endothelium, histamine caused a concentration-dependent relaxation with Imax values between 87% and 81% and pIC50 values between 8.14 and 7.15. In arteries without endothelium the histamine-induced relaxation was significantly less potent (Imax values between 87% and 66% and pIC50 values between 7.01 and 6.67) than in cranial arteries with an intact endothelium. 4. This addition of histamine to arteries without endothelium and pretreated with the histamine H2-antagonist, cimetidine (10(-5) M), caused a concentration-dependent contraction of the cranial arteries with Emax values between 86% and 29% and pEC50 values between 7.53 and 6.77. This contraction was blocked by the histamine H1-receptor antagonist, mepyramine (10(-7) M), and even turned into a relaxation with Imax values between 84% and 14% and pIC50 values between 7.42 and 5.86. 5. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 3 x 10(-5) M) significantly inhibited the relaxant response to histamine in cerebral and temporal arteries (pIC50 values between 7.43 and 7.13). The combined treatment with L-NAME (3 x 10(-5) M) and cimetidine (10(-5) M) caused a further displacement of the concentration-response curve (pIC50 values between 7.14 and 6.57) and decreased the maximum relaxant responses in all three cranial arteries (Imax values between 62% and 39%). 6. In conclusion, this is the first study which show mRNA encoding histamine H1- and H2-receptors in human cranial arteries. The results indicate that histamine-induced relaxation of human cranial arteries is partially mediated via an endothelial H1-receptor coupled to the production of nitric oxide and partially via a H2-receptor associated with the smooth muscle cells. In addition, there is evidence for a contractile H1-receptor in the smooth muscle cells in these arteries.

Cerebral Arteries↗
PubMed1998

Ca2+ mobilization in the aortic endothelium in streptozotocin-induced diabetic and cholesterol-fed mice.

1. Experiments were performed to compare Ca2+ mobilization in the aortic endothelium in streptozotocin (STZ)-induced diabetic and cholesterol-fed mice with that in age-matched controls. 2. The intracellular free Ca2+ ([Ca2+]i) in the fura PE-3 loaded endothelium of aortic rings was dose-dependently increased by cumulative administration of acetylcholine (ACh). ACh caused a transient rise in [Ca2+]i in Ca2+-free medium. The ACh-induced increase in [Ca2+]i in normal or Ca2+-free medium was significantly weaker in both STZ-induced diabetic and cholesterol-fed mice. 3. The weaker [Ca2+]i response in Ca2+-containing medium in STZ-induced diabetic and cholesterol-fed mice was normalized by chronic administration of cholestyramine. 4. The increased low density lipoprotein (LDL) levels seen in both STZ-induced diabetic and cholesterol-fed mice were normalized by the same chronic administration of cholestyramine (300 mg kg(-1), p.o. daily for 10 weeks). Chronic administration of cholestyramine had no effect on the plasma glucose level. 5. Lysophosphatidylcholine (LPC) decreased the [Ca2+]i responses to ACh in the aortic endothelium from normal mice. 6. These results suggest that ACh increases both Ca2+ influx and Ca2+ release from storage in the aortic endothelium. The weaker [Ca2+]i influx seen in the endothelium of aortae from both STZ-induced diabetic and cholesterol-fed mice was improved by the chronic administration of cholestyramine, and we suggest that this improvement is due, at least in part, to a lowering of the plasma LDL level. It is further suggested that LPC may have an important influence over Ca2+ mobilization in the endothelium.

Animals↗