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Query: UMLS:C0432222 (
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47,337
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Endothelium-derived nitric oxide (NO) plays a key role in the regulation of vascular tone in health and disease. The present study addresses the contribution of NO to the baseline vascular tone in the fetal placental circulation of type 1 diabetic women. To this end, we performed ex-vivo dual perfusions of isolated cotyledons from seven women with type 1 diabetes mellitus and 24 healthy women. The fetal arterial pressure was considered to be a measure of fetal vascular resistance. The contribution of NO to the baseline vascular tone of the fetal placental circulation was quantified by addition of the NO-synthase inhibitor N(G)-nitro-arginine-methylester (L-
NAME
). Apart from the diabetic state, we studied the influence of exogenous insulin on the response to L-
NAME
. Mean (+/-
SEM
) baseline fetal arterial pressure was higher in diabetes (25.7+/-3.4 mm Hg vs 18.0+/-1.7 mm Hg, P<0.05). Maximum perfusion pressure after L-
NAME
was 87.9+/-7.1 mm Hg in diabetes vs 58.9+/-4.5 mm Hg in controls (P<0.01). The net L-
NAME
-induced increase in fetal arterial pressure was higher in diabetes (62.2+/-9.1 mm Hg vs 40.9+/-3.5 mm Hg, P<0.05). Although insulin induced a shift to the left of the L-
NAME
-curve, the net L-
NAME
-induced increase in fetal arterial pressure was not affected. We conclude that diabetes is associated with an increased baseline vascular tone of the fetal placental vascular bed. This can not be explained by attenuated NO-mediated effects. In contrast, the activity of the NO-pathway seems to be increased in diabetes. The latter observation seems not to be caused by high insulin levels.
...
PMID:Nitric oxide-mediated vascular tone in the fetal placental circulation of patients with type 1 diabetes mellitus. 1458 Mar 80
Nitric oxide has been reported to be beneficial in preserving muscle viability following ischemia-reperfusion injury. The purpose of this study was to evaluate the influence of nitric oxide via L-arginine on leukocyte adhesion following ischemia-reperfusion injury. Intravital videomicroscopy of rat gracilis muscle was used to quantify changes in leukocyte adherence. The gracilis muscle was raised on its vascular pedicle in 48 male Wistar rats. The animals were assigned to one of five groups: (1) nonischemic control; (2) ischemia-reperfusion; (3) ischemia-reperfusion and L-arginine; (4) ischemia-reperfusion and Nomega-nitro-L-arginine methyl ester (L-
NAME
); and (5) ischemia-reperfusion, L-
NAME
, and L-arginine. All groups that included ischemia-reperfusion were subjected to 4 hours of global ischemia followed by 2 hours of reperfusion. L-Arginine (10 mg/kg) and L-
NAME
(10 mg/kg) were infused into the contralateral femoral vein beginning 5 minutes before reperfusion, for a total of 30 minutes. The number of adherent leukocytes was counted at baseline and at 5, 15, 30, 60, and 120 minutes after reperfusion (reported as mean change from baseline, +/-
SEM
). Groups were compared by repeated-measures analysis of variance (five groups, five times). P < or =0.05 was accepted as significant. L-Arginine significantly reduced leukocyte adherence to venular endothelium during reperfusion when compared with the ischemia-reperfusion group (1.39 +/- 0.92 versus 12.78 +/- 1.43 at 2 hours, p < 0.05). Administration of L-
NAME
with L-arginine showed no significant difference in adherent leukocytes when compared with the ischemia-reperfusion group (10.28 +/- 2.03 at 2 hours). The nitric oxide substrate L-arginine appears to reduce the deleterious neutrophil-endothelial adhesion associated with ischemia-reperfusion injury. L-
NAME
(nitric oxide synthesis inhibitor) given concomitantly with L-arginine reversed the beneficial effect of L-arginine alone, indicating that L-arginine may be acting via a nitric oxide synthase pathway. These results suggest an important role for nitric oxide in decreasing the neutrophil-endothelial interaction associated with ischemia-reperfusion injury.
...
PMID:Effect of L-arginine on leukocyte adhesion in ischemia-reperfusion injury. 1511 31
Nitric oxide (NO) is the mediator of ischemic preconditioning against myocardial infarction. Desflurane produces anesthetic preconditioning to protect the myocardium against infarction. In the model of myocardial ischemia-reperfusion injury in rabbits, we evaluated desflurane-induced ischemic preconditioning and studied its mechanism of NO synthesis. Thirty-two male adult New Zealand white rabbits were anesthetized with intravenous (IV) 30 mg/kg pentobarbital followed by 5 mg/kg/hr infusion. All rabbits were subjected to 30 minutes (min) long lasting left anterior descending coronary artery (LAD) occlusion and three hours (hr) of subsequent reperfusion. Before LAD occlusion, the rabbits were randomly allocated into four groups for preconditioning treatment (eight for each group). The control group did not receive any preconditioning treatment. The desflurane group received inhaled desflurane 1.0 MAC (minimal end-tidal alveolar concentration) for 30 min that was followed by a 15 min washout period. The L-
NAME
-desflurane group received L-
NAME
(NG-nitro-L-arginine methyl ester; non-selective Nitric Oxide Synthetase (NOS) inhibitor) 1 mg/kg IV 15 min before 1.0 MAC inhaled desflurane for 30 min. The L-
NAME
group received L-
NAME
1 mg/kg IV. Infarct volume, ventricular arrhythmia, plasma lactate dehydrogenase (LDH), creatine kinase (CK) activity and myocardial perfusion were recorded simultaneously. We have found that hemodynamic values of the coronary blood flow before, during, and after LAD occlusion were not significantly different among these four groups. For the myocardial ischemia-reperfusion injury animals, the infarction size (mean +/-
SEM
) in the desflurane group was significantly reduced to 18 +/- 3% in the area at risk as compared with 42 +/- 7% in the control group, 35 +/- 6 in the L-
NAME
group, and 34 +/- 4% in the L-
NAME
-desflurane group. The plasma LDH, CK levels, and duration of ventricular arrhythmia were also significantly decreased in the desflurane group during ischemia-reperfusion injury. Our results indicate that desflurane is an anesthetic preconditioning agent, which could protect the myocardium against the ischemia-reperfusion injury. This beneficial effect of desflurane on the ischemic preconditioning is probably through NO release since L-
NAME
abrogates the desflurane preconditioning effect.
...
PMID:Effect of desflurane-induced preconditioning following ischemia-reperfusion on nitric oxide release in rabbits. 1556 90
Cortical spreading depression (CSD) has been documented to confer ischemic tolerance on brain. Although nitric oxide (NO) is a crucial mediator in preconditioning under certain circumstances, the role of NO in CSD-induced neuroprotection is unclear. We examined the effect of L-
NAME
, an inhibitor of NO synthase, on CSD-induced tolerance against transient focal cerebral ischemia. A solution of 0.5 M KCl was applied for 2 h on the right hemisphere to induce CSD. Animals received either vehicle or L-
NAME
(4 mg/kg, iv) 30 min before CSD. Temporary occlusion (120 min) of the right middle cerebral artery was induced 4 days after preconditioning and the infarct volume was measured. Additionally, ERK 1/2 activation and cyclooxygenase-2 (COX-2) expression in the cerebral cortex were examined by Western blotting analysis immediately after cessation of CSD, or at 1, 2, 4, 8, and 24 h after CSD. CSD reduced infarct volume from 275 +/- 15 mm3 (mean +/-
SEM
) in the non-CSD group to 155 +/- 14 mm3 in the CSD group (P < 0.05). L-
NAME
abolished this protection (281 +/- 14 mm3; P < 0.05 vs. CSD group). Elevated ERK activation and COX-2 expression were observed immediately after or 8 h after preconditioning, respectively. Those responses are significantly augmented by L-
NAME
(3-fold for ERK and 4-fold for COX-2). These results suggest a crucial role of NO in the establishment of preconditioning with CSD.
...
PMID:The role of nitric oxide in the development of cortical spreading depression-induced tolerance to transient focal cerebral ischemia in rats. 1578 Oct 49
1. The effects of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-
NAME
) on anaphylaxis-induced venoconstriction were examined in rat isolated livers perfused with blood-free solutions in order to clarify the role of NO in anaphylactic venoconstriction. 2. Rats were sensitized with ovalbumin (1 mg) and, 2 weeks later, livers were excised and perfused portally in a recirculating manner at a constant flow with Krebs'-Henseleit solution. The antigen (ovalbumin; 0.1 mg) was injected into the reservoir 10 min after pretreatment with L-
NAME
(100 micromol/L) or D-
NAME
(100 micromol/L) and changes in portal vein pressure (Ppv), hepatic vein pressure (Phv) and perfusate flow were monitored. In addition, concentrations of the stable metabolites of NO ( and ) were determined in the perfusate using an HPLC-Griess system. 3. The antigen caused hepatic venoconstriction, as evidenced by an increase in Ppv from a mean (
SEM
) baseline value of 7.7 +/- 0.1 cmH2O to a peak of 21.4 +/- 1.1 cmH2O at 3 min in D-
NAME
-pretreated livers. Pretreatment with L-
NAME
augmented anaphylactic venoconstriction, as reflected by a higher Ppv (27.4 +/- 0.8 cmH2O) after antigen than observed following D-
NAME
pretreatment. The addition of L-arginine, a precursor for the synthesis of NO, reversed the augmentation of anaphylactic venoconstricion by L-
NAME
. This suggests that hepatic anaphylaxis increased the production of NO, which consequently attenuated anaphylactic venoconstriction. However, perfusate NOx levels did not increase significantly after antigen in livers pretreated with either L-
NAME
or D-
NAME
. 4. In conclusion, L-
NAME
potentiates rat anaphylactic hepatic venoconstriction, suggesting that NO contributes to the attenuation of the venoconstriction. However, this functional evidence was not accompanied by corresponding changes in perfusate NOx concentrations.
...
PMID:N(G)-nitro-L-arginine methyl ester potentiates anaphylactic venoconstriction in rat perfused livers. 1704 17
We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-
NAME
-induced hypertension (20 mg/kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-
NAME
for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means +/-
SEM
) 2.47 +/- 0.08 to 2.14 +/- 0.07; conscious, 7 days: from 2.85 +/- 0.13 to 2.07 +/- 0.33; anesthetized, 2 days: from 3.00 +/- 0.09 to 1.83 +/- 0.25 and anesthetized, 7 days: from 3.56 +/- 0.11 to 1.53 +/- 0.10 mmHg mL-1 min-1) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 +/- 4.5 to 96 +/- 4; anesthetized: from 118 +/- 1.5 to 104 +/- 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-
NAME
was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension.
...
PMID:Sympathetic activation in rats with L-NAME-induced hypertension. 1733 38
1. Although leptin increases sympathetic nerve activity and blood pressure, its direct action on large arterial rings is to cause relaxation. However, it is the small resistance arteries and veins that are important in blood pressure control. The effects of leptin on these small vessels has not been reported previously in the canine and the effect of leptin on the capacitance vessels is not known. 2. In the present study, third- or fourth-order canine mesenteric arteries and veins were isolated and placed in a perfusion myograph and preconstricted with noradrenaline. The responses to graded concentrations of leptin were determined and the role of nitric oxide was assessed by administration of N(G)-nitro-l-arginine methyl ester (l-
NAME
), a blocker of nitric oxide synthase. 3. Leptin induced dose-related dilatations in both arterial and venous segments. The mean (+/-
SEM
) maximum increases in the diameter of the arteries and veins were 25.0 +/- 4.8 and 29.9 +/- 2.0% of the initial preconstriction, respectively. Relaxations of both arteries and veins were abolished by l-
NAME
or by endothelium denudation, although dilatations were still obtained to sodium nitroprusside, a nitric oxide donor. 4. These results indicate that leptin dilates canine small mesenteric arteries and veins by a mechanism involving endothelial release of nitric oxide. This observation may result in a decrease of peripheral resistance and venous return and, hence, counteract the leptin-induced neurally mediated vasoconstriction that has been reported previously.
...
PMID:Vasodilator effects of leptin on canine isolated mesenteric arteries and veins. 1760 May 55
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a cerebrovascular dilator and was found neuroprotective in numerous in vitro and in vivo models of cerebral ischemia. However, the mechanism of its cerebrovascular action is poorly known, especially in newborns. Therefore, we tested pial arteriolar responses to the two naturally occurring forms PACAP27 and 38 as well as to shorter sequences (PACAP6-27, 6-38, 1-15, 6-15, 20-31). We also investigated the involvement of nitric oxide synthase (NOS), cyclooxygenase-1 and -2 (COX-1 and -2) activity in PACAP-induced pial arteriolar responses using the NOS inhibitor N-omega-nitro-l-arginine methyl ester (L-
NAME
15 mg/kg iv), the non-selective COX inhibitor indomethacin (5 mg/kg iv), and the selective COX-1 and COX-2 inhibitors SC-560 (1 mg/kg iv) and NS-398 (1 mg/kg iv), respectively. Anesthetized, ventilated piglets (n=127) were equipped with closed cranial windows, and pial arteriolar diameters were determined via intravital microscopy. Topical application of both natural PACAPs, but none of the PACAP segments, resulted in prominent, repeatable, dose-dependent vasodilation. Percentage changes ranged 5+/-1-29+/-6 (n=7) and 4+/-1-36+/-7 (n=9) to 10(-)(8) to 10(-)(6) M PACAP27 and 38 (mean+/-
SEM
), respectively. Vasodilation to both natural PACAPs was significantly reduced by co-application with PACAP6-27 or 6-38, but not by L-
NAME
. Indomethacin abolished PACAP38 but not PACAP27-induced vasodilation. Arteriolar responses to PACAP38 were also sensitive to SC-560 but not to NS-398 suggesting the unique involvement of COX-1 activity in this response. In summary, PACAP27 and 38 are potent vasodilators in the neonatal cerebral circulation with at least two distinct mechanisms of action: a COX-dependent and a COX-independent pathway.
...
PMID:Pituitary adenylate cyclase-activating polypeptide induces pial arteriolar vasodilation through cyclooxygenase-dependent and independent mechanisms in newborn pigs. 1765 92
The investigation of resistance vessels is generally costly and difficult to execute. The present study investigated the diameters and the vascular reactivity of different segments of the rat tail artery (base, middle, and tail end) of 30 male Wister rats (EPM strain) to characterize a conductance or resistance vessel, using a low-cost simple technique. The diameters (mean +/-
SEM
) of the base and middle segments were 471 +/- 4.97 and 540 +/- 8.39 microm, respectively, the tail end was 253 +/- 2.58 microm. To test reactivity, the whole tail arteries or segments were perfused under constant flow and the reactivity to phenylephrine (PHE; 0.01-300 microg) was evaluated before and after removal of the endothelium or drug administration. The maximal response (Emax) and sensitivity (pED50) to PHE of the whole tail and the base segment increased after endothelium removal or treatment with 100 microM L-
NAME
, which suggests modulation by nitric oxide. Indomethacin (10 microM) and tetraethylammonium (5 mM) did not change the Emax or pED50 of these segments. PHE and L-
NAME
increased the pED50 of the middle and the tail end only and indomethacin did not change pED50 or Emax. Tetraethylammonium increased the sensitivity only at the tail end, which suggests a blockade of vasodilator release. Results indicate that the proximal segment of the tail artery possesses a diameter compatible with a conductance vessel, while the tail end has the diameter of a resistance vessel. In addition, the vascular reactivity to PHE in the proximal segment is nitric oxide-dependent, while the tail end is dependent on endothelium-derived hyperpolarizing factor.
...
PMID:Differences in functional and structural properties of segments of the rat tail artery. 1851 69
Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective in numerous models. Impairment of cerebrovascular reactivity (CR) contributes to ischemia/reperfusion (I/R)-induced neuronal damage. We tested whether PACAP and/or VIP preserve CR to I/R-sensitive dilator responses dependent on endothelial and/or neuronal function. Accordingly, changes in pial arteriolar diameters in response to hypercapnia (5-10% CO(2) ventilation) or topical N-methyl-d-aspartate (NMDA, 10(-4) M) were determined before and after I/R via intravital microscopy in anesthetized/ventilated piglets. Local pretreatment with non-vasoactive doses of PACAP (10(-8) M) and VIP (10(-9) M) prevented the attenuation of postischemic CR to hypercapnia; to 10% CO(2), the CR values were 27+/-8% vs 92+/-5% vs 88+/-13% (vehicle vs PACAP38 vs VIP, CR expressed as a percentage of the response before I/R, mean+/-
SEM
, n=8-8, p<0.05). PACAP, but not VIP, preserved CR to NMDA after I/R, with CR values of 31+/-10% vs 87+/-8% vs 35+/-12% (vehicle vs PACAP38 vs VIP, n=6-6). Unlike PACAP, VIP-induced vasodilation has not yet been investigated in the piglet. We tested whether VIP-induced arteriolar dilation was sensitive to inhibitors of cyclooxygenase (COX)-1 (SC-560, 1 mg/kg), COX-2 (NS-398, 1 mg/kg), indomethacin (5 mg/kg), and nitric oxide synthase (L-
NAME
, 15 mg/kg). VIP (10(-8)-10(-7)-10(-6) M, n=8) induced reproducible, dose-dependent vasodilation of 16+/-3%, 33+/-6%, and 70+/-8%. The response was unaffected by all drugs, except that the vasodilation to 10(-8) M VIP was abolished by SC-560 and indomethacin. In conclusion, PACAP and VIP differentially preserve postischemic CR; independent of their vasodilatory effect.
...
PMID:PACAP and VIP differentially preserve neurovascular reactivity after global cerebral ischemia in newborn pigs. 1953 45
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