Leukocyte adherence inhibits adenosine-dependent venular control of arteriolar diameter and nitric oxide

2006 ◽  
Vol 291 (2) ◽  
pp. H724-H731 ◽  
Author(s):  
Min-ho Kim ◽  
Norman R. Harris
Keyword(s):  
Nitric Oxide ◽  
Adenosine Deaminase ◽  
Intravital Microscopy ◽  
Leukocyte Adherence ◽  
Rat Mesentery ◽  
High Adherence ◽  
Local Superfusion ◽  
Arteriolar Diameter ◽  
Adherence Group ◽  
Dependent Mechanism

Venular control of arteriolar perfusion has been the focus of several investigations in recent years. This study investigated 1) whether endogenous adenosine helps control venule-dependent arteriolar dilation and 2) whether venular leukocyte adherence limits this response via an oxidant-dependent mechanism in which nitric oxide (NO) levels are decreased. Intravital microscopy was used to assess changes in arteriolar diameters and NO levels in rat mesentery. The average resting diameter of arterioles (27.5 ± 1.0 μm) paired with venules with minimal leukocyte adherence (2.1 ± 0.3 per 100-μm length) was significantly larger than that of unpaired arterioles (24.5 ± 0.8 μm) and arterioles (23.3 ± 1.3 μm) paired with venules with higher leukocyte adherence (9.0 ± 0.5 per 100-μm length). Local superfusion of adenosine deaminase (ADA) induced significant decreases in diameter and perivascular NO concentration in arterioles closely paired to venules with minimal leukocyte adherence. However, ADA had little effect on arterioles closely paired to venules with high leukocyte adherence or on unpaired arterioles. To determine whether the attenuated response to ADA for the high-adherence group was oxidant dependent, the responses were also observed in arterioles treated with 10−4 M Tempol. In the high-adherence group, Tempol fully restored NO levels to those of the low-adherence group; however, the ADA-induced constriction remained attenuated, suggesting a possible role for an oxidant-independent vasoconstrictor released from the inflamed venules. These findings suggest that adenosine- and venule-dependent dilation of paired arterioles may be mediated, in part, by NO and inhibited by venular leukocyte adherence.

Leukocyte adhesion induced by inhibition of nitric oxide production in skeletal muscle

1995 ◽  
Vol 78 (5) ◽  
pp. 1725-1732 ◽  
Author(s):  
T. Akimitsu ◽  
D. C. Gute ◽  
R. J. Korthuis
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Leukocyte Adhesion ◽  
No Synthase ◽  
Nitric Oxide Production ◽  
Leukocyte Adherence ◽  
Synthase Inhibitor ◽  
Dependent Mechanism ◽  
Exogenous Source

Superfusion of rat cremaster muscles with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) elicited significant leukocyte adhesion to postcapillary venules (20- to 30-microns diameter), an effect that was attenuated by pretreatment with L-arginine (an NO precursor) or sodium nitroprusside (SNP) (an exogenous source of NO). In contrast to the effects of pretreatment, addition of SNP or L-arginine to the superfusate 30 min after the initiation of NO synthase inhibition failed to reverse the L-NAME-induced leukocyte adherence. However, this effect was reversed by administration of an anti-CD18 monoclonal antibody or 8-bromoguanosine 3′,5′-cyclic monophosphate 30 min after L-NAME superfusion was initiated. These findings indicate that L-NAME promotes leukocyte adhesion to venular endothelium by a CD18-dependent mechanism in skeletal muscle and suggest that the failure of L-arginine or SNP to reverse L-NAME-induced leukocyte adherence is not due to a defect in signaling events that occur subsequent to activation of guanylate cyclase by NO derived from these agents. Because the simultaneous administration of superoxide dismutase (scavenges superoxide radicals) and SNP or L-arginine, but not superoxide dismutase alone, decreased L-NAME-induced leukocyte adherence, our results suggest that leukocyte adhesion caused by NO synthase inhibition may result in the generation of superoxide.

scholarly journals Selective estrogen receptor-α and estrogen receptor-β agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism

2008 ◽  
Vol 295 (5) ◽  
pp. R1486-R1493 ◽  
Author(s):  
Tim Lahm ◽  
Paul R. Crisostomo ◽  
Troy A. Markel ◽  
Meijing Wang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Estrogen Receptor ◽  
Pulmonary Artery ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Organ Bath ◽  
Sprague Dawley ◽  
Response Curves ◽  
Vascular Effects ◽  
M 10 ◽  
Dependent Mechanism

Both endogenous and exogenous estrogen decrease pulmonary artery (PA) vasoconstriction. Whether these effects are mediated via estrogen receptor (ER)-α or ER-β, and whether the contribution of ERs is stimulus-dependent, remains unknown. We hypothesized that administration of the selective ER-α agonist propylpyrazole triol (PPT) and/or the selective ER-β agonist diarylpropiolnitrile (DPN) rapidly decreases PA vasoconstriction induced by pharmacologic and hypoxic stimuli via a nitric oxide (NO)-dependent mechanism. PA rings ( n = 3–10/group) from adult male Sprague-Dawley rats were suspended in physiologic organ baths. Force displacement was measured. Vasoconstrictor responses to phenylephrine (10−8M − 10−5M) and hypoxia (Po2 35–45 mmHg) were determined. Endothelium-dependent and -independent vasorelaxation were measured by generating dose-response curves to acetylcholine (10−8M − 10−4M) and sodium nitroprusside (10−9M − 10−5M). PPT or DPN (10−9M − 5 × 10−5M) were added to the organ bath in the presence and absence of the NO-synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) (10−4M). Selective ER-α activation (PPT, 5 × 10−5M) rapidly (<20 min) decreased phenylephrine-induced vasoconstriction. This effect, as well as PPT's effects on endothelium-dependent vasorelaxation, were neutralized by l-NAME. In contrast, selective ER-β activation (DPN, 5 × 10−5M) rapidly decreased phase II of hypoxic pulmonary vasoconstriction (HPV). l-NAME eliminated this phenomenon. Lower PPT or DPN concentrations were less effective. We conclude that both ER-α and ER-β decrease PA vasoconstriction. The immediate onset of effect suggests a nongenomic mechanism. The contribution of specific ERs appears to be stimulus specific, with ER-α primarily modulating phenylephrine-induced vasoconstriction, and ER-β inhibiting HPV. NO inhibition eliminates these effects, suggesting a central role for NO in mediating the pulmonary vascular effects of both ER-α and ER-β.

scholarly journals Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism

2006 ◽  
Vol 72 (1) ◽  
pp. 80-89 ◽  
Author(s):  
L NUNEZ ◽  
M VAQUERO ◽  
R GOMEZ ◽  
R CABALLERO ◽  
P MATEOSCACERES ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cyclic Gmp ◽  
Dependent Mechanism

scholarly journals Angiotensin-(1–7) increases neuronal potassium current via a nitric oxide-dependent mechanism

2011 ◽  
Vol 300 (1) ◽  
pp. C58-C64 ◽  
Author(s):  
Rui-Fang Yang ◽  
Jing-Xiang Yin ◽  
Yu-Long Li ◽  
Matthew C. Zimmerman ◽  
Harold D. Schultz
Keyword(s):  
Nitric Oxide ◽  
Neuronal Activity ◽  
Renin Angiotensin System ◽  
Protective Role ◽  
Patch Clamp Technique ◽  
Angiotensin System ◽  
The Central Nervous System ◽  
Nos Inhibitor ◽  
Inos Inhibition ◽  
Dependent Mechanism

Actions of angiotensin-(1–7) [Ang-(1–7)], a heptapeptide of the renin-angiotensin system, in the periphery are mediated, at least in part, by activation of nitric oxide (NO) synthase (NOS) and generation NO·. Studies of the central nervous system have shown that NO· acts as a sympathoinhibitory molecule and thus may play a protective role in neurocardiovascular diseases associated with sympathoexcitation, such as hypertension and heart failure. However, the contribution of NO in the intraneuronal signaling pathway of Ang-(1–7) and the subsequent modulation of neuronal activity remains unclear. Here, we tested the hypothesis that neuronal NOS (nNOS)-derived NO· mediates changes in neuronal activity following Ang-(1–7) stimulation. For these studies, we used differentiated catecholaminergic (CATH.a) neurons, which we show express the Ang-(1–7) receptor (Mas R) and nNOS. Stimulation of CATH.a neurons with Ang-(1–7) (100 nM) increased intracellular NO levels, as measured by 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM) fluorescence and confocal microscopy. This response was significantly attenuated in neurons pretreated with the Mas R antagonist (A-779), a nonspecific NOS inhibitor (nitro-l-arginine methyl ester), or an nNOS inhibitor ( S-methyl-l-thiocitrulline, SMTC), but not by endothelial NOS (eNOS) or inhibitory NOS (iNOS) inhibition {l- N-5-(1-iminoethyl)ornithine (l-NIO) and 1400W, respectively}. To examine the effect of Ang-(1–7)-NO· signaling on neuronal activity, we recorded voltage-gated outward K+ current ( IKv) in CATH.a neurons using the whole cell configuration of the patch-clamp technique. Ang-(1–7) significantly increased IKv, and this response was inhibited by A-779 or S-methyl-l-thiocitrulline, but not l-NIO or 1400W. These findings indicate that Ang-(1–7) is capable of increasing nNOS-derived NO· levels, which in turn, activates hyperpolarizing IKv in catecholaminergic neurons.

scholarly journals Effect of time and vascular pressure on permeability and cyclic nucleotides in ischemic lungs

2000 ◽  
Vol 279 (5) ◽  
pp. H2077-H2084 ◽  
Author(s):  
David B. Pearse ◽  
Patrice M. Becker
Keyword(s):  
Nitric Oxide ◽  
High Pressure ◽  
Reflection Coefficient ◽  
Cyclic Nucleotides ◽  
Fluid Flux ◽  
No Donor ◽  
Independent Mechanism ◽  
Dependent Mechanism ◽  
Intravascular Pressure

We previously found that increased intravascular pressure decreased ischemic lung injury by a nitric oxide (NO)-dependent mechanism (Becker PM, Buchanan W, and Sylvester JT. J Appl Physiol 84: 803–808, 1998). To determine the role of cyclic nucleotides in this response, we measured the reflection coefficient for albumin (ςalb), fluid flux ( J˙), cGMP, and cAMP in ferret lungs subjected to either 45 min (“short”; n = 7) or 180 min (“long”) of ventilated ischemia. Long ischemic lungs had “low” (1–2 mmHg, n = 8) or “high” (7–8 mmHg, n = 6) vascular pressure. Other long low lungs were treated with the NO donor ( Z)-1-[ N-(3-ammoniopropyl)- N-( n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA-NONOate; 5 × 10−4 M, n = 6) or 8-bromo-cGMP (5 × 10−4 M, n = 6). Compared with short ischemia, long low ischemia decreased ςalb (0.23 ± 0.04 vs. 0.73 ± 0.08; P < 0.05) and increased J˙ (1.93 ± 0.26 vs. 0.58 ± 0.22 ml · min−1 · 100 g−1; P < 0.05). High pressure prevented these changes. Lung cGMP decreased by 66% in long compared with short ischemia. Lung cAMP did not change. PAPA-NONOate and 8-bromo-cGMP increased lung cGMP, but only 8-bromo-cGMP decreased permeability. These results suggest that ischemic vascular injury was, in part, mediated by a decrease in cGMP. Increased vascular pressure prevented injury by a cGMP-independent mechanism that could not be mimicked by administration of exogenous NO.

scholarly journals The involvement of norepinephrine, neuropeptide Y, and nitric oxide in the cutaneous vasodilator response to local heating in humans

2008 ◽  
Vol 105 (1) ◽  
pp. 233-240 ◽  
Author(s):  
Gary J. Hodges ◽  
Wojciech A. Kosiba ◽  
Kun Zhao ◽  
John M. Johnson
Keyword(s):  
Nitric Oxide ◽  
Neuropeptide Y ◽  
Neurotransmitter Release ◽  
Local Heating ◽  
Axon Reflex ◽  
Laser Doppler Flow ◽  
Doppler Flow ◽  
Vasodilator Response ◽  
Oxide Synthase ◽  
Dependent Mechanism

Presynaptic blockade of cutaneous vasoconstrictor nerves (VCN) abolishes the axon reflex (AR) during slow local heating (SLH) and reduces the vasodilator response. In a two-part study, forearm sites were instrumented with microdialysis fibers, local heaters, and laser-Doppler flow probes. Sites were locally heated from 33 to 40°C over 70 min. In part 1, we tested whether this effect of VCN acted via nitric oxide synthase (NOS). In five subjects, treatments were as follows: 1) untreated; 2) bretylium, preventing neurotransmitter release; 3) NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS; and 4) combined bretylium + l-NAME. At treated sites, the AR was absent, and there was an attenuation of the ultimate vasodilation ( P < 0.05), which was not different among those sites ( P > 0.05). In part 2, we tested whether norepinephrine and/or neuropeptide Y is involved in the cutaneous vasodilator response to SLH. In seven subjects, treatments were as follows: 1) untreated; 2) propranolol and yohimbine to antagonize α- and β-receptors; 3) BIBP-3226 to antagonize Y1 receptors; and 4) combined propranolol + yohimbine + BIBP-3226. Treatment with propranolol + yohimbine or BIBP-3226 significantly increased the temperature at which AR occurred ( n = 4) or abolished it ( n = 3). The combination treatment consistently eliminated it. Importantly, ultimate vasodilation with SLH at the treated sites was significantly ( P < 0.05) less than at the control. These data suggest that norepinephrine and neuropeptide Y are important in the initiation of the AR and for achieving a complete vasodilator response. Since VCN and NOS blockade in combination do not have an inhibition greater than either alone, these data suggest that VCN promote heat-induced vasodilation via a nitric oxide-dependent mechanism.

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