Penicillin G Induces H+, K+-ATPase via a Nitric Oxide-Dependent Mechanism in the Rat Colonic Crypt

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.

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

Cardiovascular Research ◽

10.1016/j.cardiores.2006.06.021 ◽

2006 ◽

Vol 72 (1) ◽

pp. 80-89 ◽

Cited By ~ 55

Author(s):

L NUNEZ ◽

M VAQUERO ◽

R GOMEZ ◽

R CABALLERO ◽

P MATEOSCACERES ◽

...

Keyword(s):

Nitric Oxide ◽

Cyclic Gmp ◽

Dependent Mechanism

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

AJP Cell Physiology ◽

10.1152/ajpcell.00369.2010 ◽

2011 ◽

Vol 300 (1) ◽

pp. C58-C64 ◽

Cited By ~ 38

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.

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.5.h2077 ◽

2000 ◽

Vol 279 (5) ◽

pp. H2077-H2084 ◽

Cited By ~ 8

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.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.90412.2008 ◽

2008 ◽

Vol 105 (1) ◽

pp. 233-240 ◽

Cited By ~ 74

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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