Neurogenically derived nitrosyl factors mediate sympathetic vasodilation in the hindlimb of the rat

1997 ◽  
Vol 272 (5) ◽  
pp. H2369-H2376 ◽  
Author(s):  
R. L. Davisson ◽  
O. S. Possas ◽  
S. P. Murphy ◽  
S. J. Lewis
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Sympathetic Neurons ◽  
Specific Inhibitor ◽  
No Synthase ◽  
Systemic Administration ◽  
Sympathetic Chain ◽  
Low Intensity ◽  
Stimulation Of

Skeletal muscle vasculature of the hindlimb is innervated by a sympathetic noncholinergic vasodilator system. The aim of this study was to determine whether this vasodilator system may represent postganglionic lumbar sympathetic neurons that synthesize and release nitric oxide (NO) or related NO-containing factors. We examined whether NO synthase (NOS)-positive postganglionic lumbar nerves innervate the hindlimb vasculature of the rat and whether the hindlimb vasodilation produced by electrical stimulation of the lumbar sympathetic chain of anesthetized rats is reduced after the systemic administration of the specific inhibitor of neuronal NOS 7-nitroindazole (7-NI). Subpopulations of lumbar sympathetic cell bodies stained intensely for NOS. Postganglionic fibers and varicosities within the iliac and femoral arteries also stained for NOS. Double ligation of the lumbar chain demonstrated that NOS was transported from the cell bodies toward the peripheral terminals. Low-intensity electrical stimulation of the lumbar chain produced a pronounced hindlimb vasodilation that was markedly diminished by pretreatment with 7-NI (45 mg/kg i.v.). In contrast, the vasodilator potency of acetylcholine and S-nitrosocysteine were augmented by 7-NI. These results suggest that postganglionic lumbar sympathetic neurons may synthesize and release NO-containing factors.

scholarly journals Rise in endothelium-derived NO after stimulation of rat perivascular sympathetic mesenteric nerves

1999 ◽  
Vol 277 (3) ◽  
pp. H1027-H1035 ◽  
Author(s):  
Mauricio P. Boric ◽  
Xavier F. Figueroa ◽  
M. Verónica Donoso ◽  
Alfonso Paredes ◽  
Inés Poblete ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electrical Stimulation ◽  
Sympathetic Activity ◽  
Perfusion Pressure ◽  
Stimulus Frequency ◽  
No Synthase ◽  
No Production ◽  
No Release ◽  
Perivascular Nerves ◽  
Stimulation Of

To evaluate whether sympathetic activity induces nitric oxide (NO) production, we perfused the rat arterial mesenteric bed and measured luminally accessible norepinephrine (NE), NO, and cGMP before, during, and after stimulation of perivascular nerves. Electrical stimulation (1 min, 30 Hz) raised perfusion pressure by 97 ± 7 mmHg, accompanied by peaks of 23 ± 3 pmol NE, 445 ± 48 pmol NO, and 1 pmol cGMP. Likewise, perfusion with 10 μM NE induced vasoconstriction coupled to increased NO and cGMP release. Electrically elicited NO release depended on stimulus frequency and duration. Endothelium denudation with saponin abolished the NO peak without changing NE release. Inhibition of NO synthase with 100 μM N ω-nitro-l-arginine reduced basal NO and cGMP release and blocked the electrically stimulated and exogenous NE-stimulated NO peak while enhancing vasoconstriction. Blocking either sympathetic exocytosis with 1 μM guanethidine or α1-adrenoceptors with 30 nM prazosin abolished the electrically evoked vasoconstriction and NO release. α2-Adrenoceptor blockade with 1 μM yohimbine reduced both vasoconstriction and NO peak while increasing NE release. In summary, sympathetically released NE induces vasoconstriction, which triggers a secondary release of endothelial NO coupled to cGMP production.

NO-containing factors mediate hindlimb vasodilation produced by superior laryngeal nerve stimulation

1997 ◽  
Vol 273 (1) ◽  
pp. H234-H243 ◽  
Author(s):  
O. S. Possas ◽  
S. J. Lewis
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Electrical Stimulation ◽  
Specific Inhibitor ◽  
Superior Laryngeal Nerve ◽  
Sympathetic Nerves ◽  
No Synthase ◽  
Laryngeal Nerve ◽  
Lower Intensity ◽  
Arterial Blood

The electrical stimulation (ES) of the superior laryngeal nerve (SLN) produces reflex vasodilation in the rat hindlimb. This study determined whether this vasodilation is mediated by the release of nitric oxide (NO)-containing factors (NOF) from NO synthase (NOS)-positive postganglionic lumbar sympathetic fibers that innervate the rat hindlimb vasculature. ES of the SLN (1-10 Hz for 15 s) produced frequency-dependent reductions in mean arterial blood pressure (MAP) and hindlimb and mesenteric (MR) vascular resistances. The hindlimb vasodilation was not observed in rats in which the lumbar sympathetic trunk was transected 7-10 days previously. The falls in hindquarter vascular resistance (HQR) produced by lower intensity ES of the SLN were virtually abolished by the specific inhibitor of neuronal NOS 7-nitroindazole (7-NI, 45 mg/kg i.v.). The fall in HQR produced by 10 Hz ES of the SLN was not affected by 7-NI. The falls in MR produced by 1-10 Hz ES of the SLN were unaffected by 7-NI. Four consecutive episodes of ES at 10 Hz produced pronounced and equivalent reductions in MAP, HQR, and MR. After administration of 7-NI, the first ES produced similar hemodynamic responses to those observed before injection. However, each subsequent ES produced progressively and markedly smaller falls in HQR, whereas each episode of ES produced similar falls in MR. These results suggest that the reflex vasodilation in the rat hindlimb produced by ES of the SLN involves the release of newly synthesized and performed stores of NOF from NOS-positive postganglionic lumbar sympathetic nerves.

scholarly journals Hypercapnia Relaxes Cerebral Arteries and Potentiates Neurally-Induced Relaxation

1996 ◽  
Vol 16 (5) ◽  
pp. 1068-1074 ◽  
Author(s):  
Noboru Toda ◽  
Kazuhide Ayajiki ◽  
Tomio Okamura
Keyword(s):  
Nitric Oxide ◽  
Electrical Stimulation ◽  
Cerebral Arteries ◽  
No Synthase ◽  
Chemical Stimulation ◽  
Intracellular Acidosis ◽  
Relaxant Response ◽  
Prostaglandin F ◽  
Synthase Inhibitor ◽  
Stimulation Of

The present study was designed to determine whether relaxations induced by hypercapnia depend upon nitric oxide (NO) derived from the endothelium, and whether NO-mediated relaxant response to electrical and chemical stimulation of vasodilator nerves is modulated by hypercapnia. In canine and monkey cerebral arterial strips contracted with K+, raising the level of CO2 of the aerating gas in the bathing media from 5 to 10% produced a moderate relaxation, together with an increased Pco2 (from 29.8 to 59.3 mm Hg) and a decreased pH (from 7.43 to 7.15). Relaxation was not influenced by endothelium denudation and treatment with NG-nitro-L-arginine. Contractions elicited by the NO synthase inhibitor were attenuated by the removal of the endothelium. Relaxations, caused by transmural electrical stimulation and nicotine, of canine cerebral arterial strips contracted with prostaglandin F2α were potentiated only slightly by hypercapnia, but the potentiation of the response to exogenous NO (acidified NaNO2) was clearly greater. It is concluded that as far as the arteries used are concerned, hypercapnia does not seem to liberate NO from the endothelium but does potentiate the effect of NO. The reason for lesser potentiation, by hypercapnia, of the response to nitroxidergic nerve stimulation than to NO action may be associated with an impairment by intracellular acidosis of NO synthase activation.

SOME ASPECTS OF MECHANISM OF SUCCINAMIDES INFLUENCE ON METABOLIC HOMEOSTASIS OF THE ORGANISM

2018 ◽  
pp. 27-31
Author(s):  
I. A. Palagina
Keyword(s):  
Nitric Oxide ◽  
Biological Activity ◽  
Antioxidant System ◽  
No Synthase ◽  
Antioxidant Potential ◽  
Metabolic Homeostasis ◽  
Energetic Metabolism ◽  
Complex Action ◽  
Energy Processes ◽  
Stimulation Of

Succinate containing compounds possess many types of biological activity and are used for the development of drugs with the target and complex action. This paper is devoted to some aspects of the mechanism of succinamides’ action in a dose of 100 mg/kg. We studied the influence of the compound with antidiabetic properties, -phenylethylamide of 2-oxysuccinanyl acid ( -PhEA-OSAA), and its metabolites such as 2-hydroxyphenylsuccinamide (2-HPhSA) and β-phenylethylsuccinamide ( -PhESA) on the marker indicators of energetic metabolism (EM), antioxidant system (AOS) and nitric oxide (NO) metabolism in subacute experiment on rats. Studies have shown that the action of -FEA-OSAKA on metabolic homeostasis is realized through stimulation of EM, reduction of intensity of NO-synthase metabolism and weakening of the AOS. The nature of the action of -FES and 2-GFS, taking into account the indicators of the state of homeostasis, largely coincides with β-FEA-OSAKA. It was found that the key links in the mechanism of toxic action of succinamides are the effect on antioxidant potential, NO metabolism and energy processes.

On the Respective Roles of Nitric Oxide and Carbon Monoxide in Long-Term Potentiation in the Hippocampus

1999 ◽  
Vol 6 (1) ◽  
pp. 63-76 ◽  
Author(s):  
Min Zhuo ◽  
Jarmo T. Laitinen ◽  
Xiao-Ching Li ◽  
Robert D. Hawkins
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Guanylyl Cyclase ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
No Synthase ◽  
Term Potentiation ◽  
Stimulation Of

Perfusion of hippocampal slices with an inhibitor nitric oxide (NO) synthase blocked induction of long-term potentiation (LTP) produced by a one-train tetanus and significantly reduced LTP by a two-train tetanus, but only slightly reduced LTP by a four-train tetanus. Inhibitors of heme oxygenase, the synthetic enzyme for carbon monoxide (CO), significantly reduced LTP by either a two-train or four-train tetanus. These results suggest that NO and CO are both involved in LTP but may play somewhat different roles. One possibility is that NO serves a phasic, signaling role, whereas CO provides tonic, background stimulation. Another possibility is that NO and CO are phasically activated under somewhat different circumstances, perhaps involving different receptors and second messengers. Because NO is known to be activated by stimulation of NMDA receptors during tetanus, we investigated the possibility that CO might be activated by stimulation of metabotropic glutamate receptors (mGluRs). Consistent with this idea, long-lasting potentiation by the mGluR agonist tACPD was blocked by inhibitors of heme oxygenase but not NO synthase. Potentiation by tACPD was also blocked by inhibitors of soluble guanylyl cyclase (a target of both NO and CO) or cGMP-dependent protein kinase, and guanylyl cyclase was activated by tACPD in hippocampal slices. However, biochemical assays indicate that whereas heme oxygenase is constitutively active in hippocampus, it does not appear to be stimulated by either tetanus or tACPD. These results are most consistent with the possibility that constitutive (tonic) rather than stimulated (phasic) heme oxygenase activity is necessary for potentiation by tetanus or tACPD, and suggest that mGluR activation stimulates guanylyl cyclase phasically through some other pathway.

ATP concentrations and muscle tension increase linearly with muscle contraction

2003 ◽  
Vol 95 (2) ◽  
pp. 577-583 ◽  
Author(s):  
Jianhua Li ◽  
Nicholas C. King ◽  
Lawrence I. Sinoway
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Muscle Contraction ◽  
Motor Nerve ◽  
Muscle Tension ◽  
Nerve Fibers ◽  
Ventral Root ◽  
Ventral Roots ◽  
Root Stimulation ◽  
Stimulation Of

Previous studies have suggested that activation of ATP-sensitive P2X receptors in skeletal muscle play a role in mediating the exercise pressor reflex (Li J and Sinoway LI. Am J Physiol Heart Circ Physiol 283: H2636–H2643, 2002). To determine the role ATP plays in this reflex, it is necessary to examine whether muscle interstitial ATP (ATPi) concentrations rise with muscle contraction. Accordingly, in this study, muscle contraction was evoked by electrical stimulation of the L7 and S1 ventral roots of the spinal cord in 12 decerebrate cats. Muscle ATPi was collected from microdialysis probes inserted in the muscle. ATP concentrations were determined by the HPLC method. Electrical stimulation of the ventral roots at 3 and 5 Hz increased mean arterial pressure by 13 ± 2 and 16 ± 3 mmHg ( P < 0.05), respectively, and it increased ATP concentration in contracting muscle by 150% ( P < 0.05) and 200% ( P < 0.05), respectively. ATP measured in the opposite control limb did not rise with ventral root stimulation. Section of the L7 and S1 dorsal roots did not affect the ATPi seen with 5-Hz ventral root stimulation. Finally, ventral roots stimulation sufficient to drive motor nerve fibers did not increase ATP in previously paralyzed cats. Thus ATPi is not largely released from sympathetic or motor nerves and does not require an intact afferent reflex pathway. We conclude that ATPi is due to the release of ATP from contracting skeletal muscle cells.

Synthesis and action of nitric oxide in rat glomerular mesangial cells

1991 ◽  
Vol 261 (4) ◽  
pp. F600-F606 ◽  
Author(s):  
P. J. Shultz ◽  
M. A. Tayeh ◽  
M. A. Marletta ◽  
L. Raij
Keyword(s):  
Nitric Oxide ◽  
Culture Medium ◽  
Mesangial Cells ◽  
Culture Media ◽  
Degradation Products ◽  
Specific Inhibitor ◽  
Cgmp Level ◽  
Glomerular Mesangial Cells ◽  
Intracellular Cgmp ◽  
Stimulation Of

Macrophages and certain tumor cell lines can be induced to synthesize nitric oxide (NO) from L-arginine after stimulation with lipopolysaccharide (LPS) or cytokines. In the present study, we have found that culture medium collected after 24 h from unstimulated rat mesangial cells (MC) contains 6.3 +/- 1.2 microM of NO3-/NO2- (the degradation products of NO). These levels were significantly increased when MC were incubated with LPS (10 micrograms/ml) for 24 h (23.9 +/- 4.1, P less than 0.05). The specific inhibitor of NO synthesis, NG-monomethyl-L-arginine (L-NMMA) completely inhibited LPS-stimulated production of NO3-/NO2-, confirming that the NO3-/NO2- was derived from NO within the MC. Recent studies suggest that endothelium-derived relaxing factor (EDRF) produced by vascular endothelium is also NO, and we have previously shown that both EDRF and NO stimulate increases in MC guanosine 3',5'-cyclic monophosphate (cGMP). Thus we sought to determine whether NO synthesized by the MC could affect cGMP levels within the same cells. After 24-h incubation with LPS (10 micrograms/ml), intracellular cGMP level within the MC was 706.3 +/- 197 (SE) compared with 40.5 +/- 7 fmol/micrograms protein in control MC incubated in media alone (P less than 0.01). The changes in cGMP in response to LPS were inhibited by greater than 90% by L-NMMA. Similar to LPS, incubation of MC with the cytokine gamma-interferon also increased NO3-/NO2- in the culture media and increased cGMP levels within MC. The induction of NO synthesis within MC and the concomitant stimulation of MC cGMP may be important in the modulation of the effects of endotoxemia, as well as inflammation, within the glomerulus.

Release of nitric oxide and prostaglandin H2 to acetylcholine in skeletal muscle venules

1997 ◽  
Vol 272 (6) ◽  
pp. H2541-H2546 ◽  
Author(s):  
G. Dornyei ◽  
G. Kaley ◽  
A. Koller
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Perfusion Pressure ◽  
Thromboxane A2 ◽  
No Synthase ◽  
Gracilis Muscle ◽  
Vasoactive Agents ◽  
Before And After ◽  
Higher Doses

The role of endothelium in regulating venular resistance is not well characterized. Thus we aimed to elucidate the endothelium-derived factors involved in the mediation of responses of rat gracilis muscle venules to acetylcholine (ACh) and other vasoactive agents. Changes in diameter of perfusion pressure (7.5 mmHg)- and norepinephrine (10(-6) M)-constricted venules (approximately 225 microns in diam) to cumulative doses of ACh (10(-9) to 10(-4) M) and sodium nitroprusside (SNP, 10(-9) to 10(-4) M), before and after endothelium removal or application of various inhibitors, were measured. Lower doses of ACh elicited dilations (up to 42.1 +/- 4.7%), whereas higher doses of ACh resulted in smaller dilations or even constrictions. Endothelium removal abolished both ACh-induced dilation and constriction. In the presence of indomethacin (2.8 x 10(-5) M), a cyclooxygenase blocker, or SQ-29548 (10(-6) M), a thromboxane A2-prostaglandin H2 (PGH2) receptor antagonist, higher doses of ACh caused further dilation (up to 72.7 +/- 7%) instead of constriction. Similarly, lower doses of arachidonic acid (10(-9) to 10(-6) M) elicited dilations that were diminished at higher doses. These reduced responses were, however, reversed to substantial dilation by SQ-29548. The nitric oxide (NO) synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), significantly reduced the dilation to ACh (from 30.6 +/- 5.5 to 5.4 +/- 1.4% at 10(-6) M ACh). In contrast, L-NNA did not affect dilation to SNP. Thus ACh elicits the release of both NO and PGH2 from the venular endothelium.

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