scholarly journals Major Role of Nitric Oxide in the Mediation of Regional CO2 Responsiveness of the Cerebral and Spinal Cord Vessels of the Cat

1994 ◽  
Vol 14 (1) ◽  
pp. 49-58 ◽  
Author(s):  
P. Sandor ◽  
K. Komjati ◽  
M. Reivich ◽  
I. Nyary
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Large Dose ◽  
Regional Blood Flow ◽  
No Synthase ◽  
Simultaneous Administration ◽  
Selective Blockade ◽  
Spinal Cord Regions ◽  
Dose Dependent

The role of nitric oxide (NO) in the mediation of cerebrovascular CO2 responsiveness was studied in 10 distinct brain and spinal cord regions of the anesthetized, ventilated, temperature-controlled, normoxic cat. Regional CBF was measured with 15-μm radiolabeled microspheres in hypocapnic, normocapnic, and hypercapnic conditions. CO2 responsiveness of each region was determined from the equation of the best-fit regression lines to the obtained flow values. The effect of altered endothelial and/or neuronal NO synthesis on CO2 responsiveness was studied following either selective blockade of the NO synthase enzyme by Nω-nitro-L-arginine methyl ester (L-NAME; 3 or 30 mg/kg i.v.) or simultaneous administration of L-NAME (3 mg/kg i.v.) and a large dose of the NO precursor L-arginine (30 mg/kg i.v.). Blockade of NO synthesis by 30 mg/kg L-NAME resulted in a significant reduction of the steady-state regional blood flow values and in an almost complete abolition of the CO2 sensitivity in each region studied. Changes of the basal flow values as well as the reduction of the regional CO2 sensitivity were dose dependent. Hypothalamic, sensorimotor cortical, and cerebellar regions were the areas most sensitive to the NO blockade. Impaired CO2 responsiveness following NO synthase inhibition, however, was reversed in these regions by simultaneous administration of a large dose of intravenously injected L-arginine. These findings suggest a major role of nitric oxide in the mediation of regional cerebrovascular CO2 responsiveness in cats.

Role of nitric oxide and superoxide anion in spontaneous lung chemiluminescence

1997 ◽  
Vol 272 (2) ◽  
pp. L262-L267 ◽  
Author(s):  
M. L. Barnard ◽  
B. Robertson ◽  
B. P. Watts ◽  
J. F. Turrens
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Light Emission ◽  
No Synthase ◽  
O2 Concentration ◽  
Dose Dependent Fashion ◽  
Spontaneous Chemiluminescence ◽  
Oxidant Production ◽  
Dose Dependent

Inhibition of nitric oxide (.NO) synthase by nitro-L-arginine (NLA) decreased baseline chemiluminescence in a dose-dependent fashion up to 78% at 300 microM NLA. This inhibition was prevented by pretreatment with 1 mM arginine. Similarly, addition of superoxide dismutase (SOD; 200 U/ml) to the perfusion buffer inhibited spontaneous light emission by 57%. Addition of NLA after SOD or vice versa did not inhibit light emission any further, suggesting that both .NO and O2.- were precursors of the same oxidant. Production of additional extracellular O2.- by neutrophils activated with phorbol 12-myristate 13-acetate increased light emission by >200%, but this increase was insensitive to NLA. Increasing the intracellular steady-state O2.- concentration by perfusion of control lungs with the Cu and Zn-containing SOD inhibitor diethyldithiocarbamate (1 mM) stimulated light emission up to fourfold, but this spontaneous chemiluminescence was also insensitive to NLA. In experiments using cultured endothelial cells supplemented with extracellular bovine serum albumin (BSA), 5 microM of the Ca2+ ionophore A-23187 (a stimulant of .NO synthase) stimulated chemiluminescence by 40%. This increase was again SOD and NLA sensitive. Addition of NLA after SOD or vice versa did not change light emission. These results suggest that the background chemiluminescence of isolated-perfused intact lungs may result from the constant release of small amounts of O2.- and .NO by endothelial cells into the capillary lumen, which in turn react with BSA in the perfusion buffer.

The role of nitric oxide in the development of neurogenic pulmonary edema in spinal cord-injured rats: the effect of preventive interventions

2009 ◽  
Vol 297 (4) ◽  
pp. R1111-R1117 ◽  
Author(s):  
Jiří Šedý ◽  
Josef Zicha ◽  
Jaroslav Kuneš ◽  
Aleš Hejčl ◽  
Eva Syková
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Spinal Cord ◽  
Heart Rate ◽  
Pulmonary Edema ◽  
No Synthase ◽  
Neurogenic Pulmonary Edema ◽  
Therapeutic Effects ◽  
Cord Injury

Neurogenic pulmonary edema (NPE) is an acute life-threatening complication following an injury of the spinal cord or brain, which is associated with sympathetic hyperactivity. The role of nitric oxide (NO) in NPE development in rats subjected to balloon compression of the spinal cord has not yet been examined. We, therefore, pretreated Wistar rats with the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) either acutely (just before the injury) or chronically (for 4 wk prior to the injury). Acute (but not chronic) l-NAME administration enhanced NPE severity in rats anesthetized with 1.5% isoflurane, leading to the death of 83% of the animals within 10 min after injury. Pretreatment with either the ganglionic blocker pentolinium (to reduce blood pressure rise) or the muscarinic receptor blocker atropine (to lessen heart rate decrease) prevented or attenuated NPE development in these rats. We did not observe any therapeutic effects of atropine administered 2 min after spinal cord compression. Our data indicate that NPE development is dependent upon a marked decrease of heart rate under the conditions of high blood pressure elicited by the activation of the sympathetic nervous system. These hemodynamic alterations are especially pronounced in rats subjected to acute NO synthase inhibition. In conclusion, nitric oxide has a partial protective effect on NPE development because it attenuates sympathetic vasoconstriction and consequent baroreflex-induced bradycardia following spinal cord injury.

Systemic and regional hemodynamics after nitric oxide synthase inhibition: role of a neurogenic mechanism

1994 ◽  
Vol 267 (1) ◽  
pp. R84-R88 ◽  
Author(s):  
M. Huang ◽  
M. L. Leblanc ◽  
R. L. Hester
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Output ◽  
No Synthase ◽  
Before And After ◽  
Regional Hemodynamics ◽  
Autonomic Blockade ◽  
Infusion Of Norepinephrine ◽  
Oxide Synthase

The study tested the hypothesis that the increase in blood pressure and decrease in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control blood pressure was measured for 30 min. Cardiac output and tissue flows were measured with radioactive microspheres. All measurements of pressure and flows were made before and after NO synthase inhibition (20 mg/kg L-NAME) in a group of control animals and in a second group of animals in which the autonomic nervous system was blocked by 20 mg/kg hexamethonium. In this group of animals, an intravenous infusion of norepinephrine (20-140 ng/min) was used to maintain normal blood pressure. L-NAME treatment resulted in a significant increase in mean arterial pressure in both groups. L-NAME treatment decreased cardiac output approximately 50% in both the intact and autonomic blocked animals (P < 0.05). Autonomic blockade alone had no effect on tissue flows. L-NAME treatment caused a significant decrease in renal, hepatic artery, stomach, intestinal, and testicular blood flow in both groups. These results demonstrate that the increase in blood pressure and decreases in cardiac output and tissue flows after L-NAME treatment are not dependent on a neurogenic mechanism.

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.

Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels

1997 ◽  
Vol 92 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Masanari Shiramoto ◽  
Tsutomu Imaizumi ◽  
Yoshitaka Hirooka ◽  
Toyonari Endo ◽  
Takashi Namba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Dependent Manner ◽  
Human Forearm ◽  
Before And After ◽  
Dose Dependent

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

Functional heterogeneity of endothelial P2 purinoceptors in the cerebrovascular tree of the rat

1999 ◽  
Vol 277 (3) ◽  
pp. H893-H900 ◽  
Author(s):  
Junping You ◽  
T. David Johnson ◽  
Sean P. Marrelli ◽  
Robert M. Bryan
Keyword(s):  
Cerebral Arteries ◽  
No Synthase ◽  
Third Order ◽  
Selective Agonist ◽  
Middle Cerebral Arteries ◽  
Spontaneous Tone ◽  
A Minor ◽  
Calcium Activated Potassium Channel ◽  
Dose Dependent

The effects of stimulating P2Y1 or P2Y2 purinoceptors on the endothelium of isolated middle cerebral arteries (MCAs), third-order branches of the MCA (bMCAs), and penetrating arterioles (PAs) of the rat were studied. After pressurization and development of spontaneous tone (25% contraction), resting diameters for MCAs, bMCAs, and PAs were 203 ± 5 ( n = 50), 99 ± 2 ( n = 42), and 87 ± 2 μm ( n = 53), respectively. Luminal application of the P2Y1-selective agonist 2-methylthioadenosine 5′-triphosphate elicited dose-dependent dilations (or loss of intrinsic tone) in MCAs but not in bMCAs or PAs. The dilation in MCAs was completely blocked by removal of the endothelium or by nitro-l-arginine methyl ester (10−5 M), an inhibitor of NO synthase. Luminal application of the P2Y2-selective agonist ATP elicited dilations in MCAs, bMCAs, and PAs. Removal of the endothelium abolished the dilations in all vessel groups. Dilations in MCAs have been shown to involve both NO and endothelium-derived hyperpolarizing factor (EDHF). The dilations in bMCAs and PAs had a minor NO component and prominent EDHF component; that is, 1) the dilations to ATP were not diminished by the combined inhibition of NO synthase and cyclooxygenase, 2) the dilations were accompanied by significant hyperpolarizations of the vascular smooth muscle (∼15 mV), and 3) the dilations were completely abolished by the calcium-activated potassium channel blocker charybdotoxin. We concluded that the role of NO in purinoceptor-induced dilations diminishes along the cerebrovascular tree in the rat, whereas the role of EDHF becomes more prominent.

Is nitric oxide the final mediator regulating the migrating myoelectric complex cycle?

1995 ◽  
Vol 268 (2) ◽  
pp. G207-G214 ◽  
Author(s):  
A. Rodriguez-Membrilla ◽  
V. Martinez ◽  
M. Jimenez ◽  
E. Gonalons ◽  
P. Vergara
Keyword(s):  
Nitric Oxide ◽  
Small Intestine ◽  
Motor Pattern ◽  
No Synthase ◽  
Phase Iii ◽  
Motor Patterns ◽  
No Donor ◽  
Postprandial State ◽  
Synthase Inhibitor

The main objective was to study the role of nitric oxide (NO) in the conversion of migrating myoelectric complexes (MMC) to the irregular electrical activity characteristic of the postprandial state. Both rats and chickens were implanted with electrodes for electromyography in the small intestine. Intravenous infusion of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, induced an organized MMC-like pattern in fed rats. Infusion of sodium nitroprusside, a NO donor, disrupted the MMC, inducing a postprandial-like motor pattern in fasting rats. Similarly, in chickens L-NNA mimicked the fasting pattern, consisting of a shortening of phase II, enlargement of phase III, orad displacement of the origin of the MMC, and an increase in the speed of phase III propagation. An inhibition of NO synthesis seems to be involved in the induction of the fasting motor pattern, whereas an increase of NO mediates the occurrence of the fed pattern. It is suggested that NO might be the final mediator in the control of small intestine motor patterns.

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