Effect of nitric oxide synthase inhibition on hypercapnia-induced hypothermia and hyperventilation

1998 ◽  
Vol 85 (3) ◽  
pp. 967-972 ◽  
Author(s):  
Renata C. H. Barros ◽  
Luiz G. S. Branco
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Body Temperature ◽  
Respiratory Function ◽  
Breathing Pattern ◽  
Ventilatory Response ◽  
No Synthase ◽  
Induced Hypothermia ◽  
Control Situation ◽  
Oxide Synthase

Hypercapnia elicits hypothermia in a number of vertebrates, but the mechanisms involved are not well understood. In the present study, we assessed the participation of the nitric oxide (NO) pathway in hypercapnia-induced hypothermia and hyperventilation by means of NO synthase inhibition by using N ω-nitro-l-arginine (l-NNA). Measurements of ventilation, body temperature, and oxygen consumption were performed in awake unrestrained rats before and afterl-NNA injection (intraperitoneally) and l-NNA injection followed by hypercapnia (5% CO2). Control animals received saline injections. l-NNA altered the breathing pattern during the control situation but not during hypercapnia. A significant ( P < 0.05) drop in body temperature was measured after bothl-NNA (40 mg/kg) and 5% inspired CO2, with a drop in oxygen consumption in the first situation but not in the second. Hypercapnia had no effect onl-NNA-induced hypothermia. The ventilatory response to hypercapnia was not changed byl-NNA, even thoughl-NNA caused a drop in body temperature. The present data indicate that the two responses elicited by hypercapnia, i.e., hyperventilation and hypothermia, do not share NO as a common mediator. However, thel-arginine-NO pathway participates, although in an unrelated way, in respiratory function and thermoregulation.

Role of the nitric oxide pathway in hypoxia-induced hypothermia of rats

1997 ◽  
Vol 273 (3) ◽  
pp. R967-R971 ◽  
Author(s):  
L. G. Branco ◽  
E. C. Carnio ◽  
R. C. Barros
Keyword(s):  
Nitric Oxide ◽  
Body Temperature ◽  
No Synthase ◽  
Regulatory Mechanisms ◽  
Induced Hypothermia ◽  
The Third ◽  
Significant Difference ◽  
Before And After ◽  
Nitric Oxide Pathway

Hypothermia is a response to hypoxia that occurs in organisms ranging from protozoans to mammals, but very little is known about the mechanisms involved. Recently, the NO pathway has been suggested to be involved in thermoregulation. In the present study, we assessed the participation of nitric oxide in hypoxia-induced hypothermia by means of NO synthase inhibition using NG-nitro-L-arginine methyl ester (L-NAME). The rectal temperature of awake, unrestrained rats was measured before and after hypoxia or L-NAME injection or both treatments together. Control animals received saline injections of the same volume. We observed a significant (P < 0.05) reduction in body temperature of 1.32 +/- 0.36 degrees C after hypoxia (7% inspired O2) and of 0.96 +/- 0.42 degree C after L-NAME (30 mg/kg body wt) injected intravenously. When the two treatments were combined, no significant difference in body temperature was observed. To assess the role of central thermo-regulatory mechanisms, a smaller dose of L-NAME (1 mg/kg) was injected into the third cerebral ventricle or intravenously. Intracerebroventricular injection of L-NAME caused an increase in body temperature, but when L-NAME was combined with hypoxia (7% inspired O2) no change in body temperature was observed. Intravenous injection of 1 mg/kg L-NAME had no effect. The data indicate that NO plays a major role in hypoxia-induced hypothermia at central rather than peripheral sites.

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.

scholarly journals Oxygen consumption in the kidney: Effects of nitric oxide synthase isoforms and angiotensin II

2005 ◽  
Vol 68 (2) ◽  
pp. 723-730 ◽  
Author(s):  
Aihua Deng ◽  
Cynthia M. Miracle ◽  
Jorge M. Suarez ◽  
Mark Lortie ◽  
Joseph Satriano ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Oxide Synthase

Capillary hydraulic conductivity is decreased by nitric oxide synthase inhibition

1995 ◽  
Vol 268 (5) ◽  
pp. H1856-H1861 ◽  
Author(s):  
R. E. Rumbaut ◽  
M. K. McKay ◽  
V. H. Huxley
Keyword(s):  
Nitric Oxide ◽  
Hydraulic Conductivity ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
Capillary Water ◽  
Cell Monolayers ◽  
Study Support ◽  
Oxide Synthase

Nitric oxide (NO) has been reported to modulate microvascular permeability to solutes in whole organs, venules, and cultured endothelial cell monolayers. NO derived from L-arginine via NO synthase activates soluble guanylate cyclase in vascular smooth muscle and endothelial cells. While the effects of NO on capillary water permeability have not been characterized, other activators of guanylate cyclase, such as sodium nitroprusside and atrial natriuretic peptide, increase capillary hydraulic conductivity (Lp). We hypothesized that inhibition of NO synthase with the arginine analogue, NG-monomethyl-L-arginine (L-NMMA), would decrease Lp from control levels. Lp was assessed in situ in single perfused frog mesenteric capillaries, first during control conditions (Lcontrolp) and then during superfusion (Ltestp) with either L-NMMA, NG-monomethyl-D-arginine (D-NMMA), a biologically inert enantiomer, or L-NMMA and L-arginine. Superfusion with 1 microM L-NMMA caused a decrease in Lp (Ltestp/Lcontrolp = 0.6 +/- 0.1, P < 0.001), whereas 1 microM D-NMMA was without effect on Lp (Ltestp/Lcontrolp = 1.0 +/- 0.2). The decrease in Lp by 1 microM L-NMMA was not only prevented by the presence of excess L-arginine (100 microM), but Lp increased from control (Ltestp/Lcontrolp = 1.4 +/- 0.2, P < 0.05). Furthermore, superfusion of L-arginine (100 microM) caused an increase in capillary Lp (Ltestp/Lcontrolp = 2.4 +/- 0.9, P < 0.05), whereas D-arginine had no effect on Lp (Ltestp/Lcontrolp = 1.2 +/- 0.3). The results of this study support our hypothesis that inhibition of NO synthase decreases capillary Lp in the intact circulation. In addition, L-arginine increases capillary Lp in our model.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium regulates estrogen increase in permeability of cultured CaSki epithelium by eNOS-dependent mechanism

2000 ◽  
Vol 279 (5) ◽  
pp. C1495-C1505 ◽  
Author(s):  
George I. Gorodeski
Keyword(s):  
Nitric Oxide ◽  
Endothelial Nitric Oxide Synthase ◽  
Cytosolic Calcium ◽  
No Synthase ◽  
Calcium Dependent ◽  
Steady State Levels ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Dependent Mechanism

Estrogen increases baseline transepithelial permeability across CaSki cultures and augments the increase in permeability in response to hypertonic gradients. In estrogen-treated cells, lowering cytosolic calcium abrogated the hypertonicity-induced augmented increase in permeability and decreased baseline permeability to a greater degree than in estrogen-deprived cells. Steady-state levels of cytosolic calcium in estrogen-deprived cells were higher than in estrogen-treated cells. Increases in extracellular calcium increased cytosolic calcium more in estrogen-deprived cells than in estrogen-treated cells. However, in estrogen-treated cells, increasing cytosolic calcium was associated with greater increases in permeability in response to hypertonic gradients than in estrogen-deprived cells. Lowering cytosolic calcium blocked the estrogen-induced increase in nitric oxide (NO) release and in the in vitro conversion of l-[3H]arginine to l-[3H]citrulline. Treatment with estrogen upregulated mRNA of the NO synthase isoform endothelial nitric oxide synthase (eNOS). These results indicate that cytosolic calcium mediates the responses to estrogen and suggest that the estrogen increase in permeability and the augmented increase in permeability in response to hypertonicity involve an increase in NO synthesis by upregulation of the calcium-dependent eNOS.

Regulation of endothelial nitric oxide synthase mRNA, protein, and activity during cell growth

1994 ◽  
Vol 267 (5) ◽  
pp. C1381-C1388 ◽  
Author(s):  
J. F. Arnal ◽  
J. Yamin ◽  
S. Dockery ◽  
D. G. Harrison
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Endothelial Nitric Oxide Synthase ◽  
Northern Blot Analysis ◽  
No Synthase ◽  
Proliferating Cells ◽  
Bovine Endothelial Cells ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Cell growth influences the expression of several important tissue-specific functions. We sought to examine the effect of cell proliferation on nitric oxide (NO) synthase gene expression in cultured aortic bovine endothelial cells. Western and Northern blot analysis revealed three- and sixfold increases in NO synthase protein and mRNA, respectively, in growing compared with growth-arrested cells. The release of nitrogen oxides was also increased in proliferating cells compared with growth-arrested cells, as was the NO synthase activity assessed by L-arginine/L-citrulline conversion. Neither NO synthase inhibitors nor superoxide dismutase affected proliferation or thymidine incorporation, suggesting that increased NO release had no effect on endothelial cell growth. In conclusion, these studies demonstrate that expression of endothelial cell NO synthase is markedly increased in proliferating compared with quiescent nongrowing cells. The mechanisms underlying this and its physiological consequences remain to be defined.

scholarly journals Potentiation of hypoxic ventilatory response by hyperoxia in the conscious rat: putative role of nitric oxide

1998 ◽  
Vol 85 (1) ◽  
pp. 129-132 ◽  
Author(s):  
David Gozal
Keyword(s):  
Nitric Oxide ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Hypoxic Ventilatory Response ◽  
Sprague Dawley ◽  
Conscious Rat ◽  
Adult Rats ◽  
Hyperoxic Exposure ◽  
Essential Components ◽  
Oxide Synthase

In humans, the hypoxic ventilatory response (HVR) is augmented when preceded by a short hyperoxic exposure (Y. Honda, H. Tani, A. Masuda, T. Kobayashi, T. Nishino, H. Kimura, S. Masuyama, and T. Kuriyama. J. Appl. Physiol. 81: 1627–1632, 1996). To examine whether neuronal nitric oxide synthase (nNOS) is involved in such hyperoxia-induced HVR potentiation, 17 male Sprague-Dawley adult rats underwent hypoxic challenges (10% O2-5% CO2-balance N2) preceded either by 10 min of room air (−O2) or of 100% O2(+O2). At least 48 h later, similar challenges were performed after the animals received the selective nNOS inhibitor 7-nitroindazole (25 mg/kg ip). In −O2 runs, minute ventilation (V˙e) increased from 121.3 ± 20.5 (SD) ml/min in room air to 191.7 ± 23.8 ml/min in hypoxia ( P< 0.01). After +O2,V˙e increased from 114.1 ± 19.8 ml/min in room air to 218.4 ± 47.0 ml/min in hypoxia (+O2 vs. −O2: P < 0.005, ANOVA). After 7-nitroindazole administration, HVR was not affected in the −O2 treatment group withV˙e increasing from 113.7 ± 17.8 ml/min in room air to 185.8 ± 35.0 ml/min in hypoxia ( P < 0.01). However, HVR potentiation in +O2-exposed animals was abolished (111.8 ± 18.0 ml/min in room air to 184.1 ± 35.6 ml/min in hypoxia; +O2 vs. −O2: P not significant). We conclude that in the conscious rat nNOS activation mediates essential components of the HVR potentiation elicited by a previous short hyperoxic exposure.

Characterization and localization of endothelial nitric oxide synthase using specific monoclonal antibodies

1993 ◽  
Vol 265 (5) ◽  
pp. C1379-C1387 ◽  
Author(s):  
J. S. Pollock ◽  
M. Nakane ◽  
L. D. Buttery ◽  
A. Martinez ◽  
D. Springall ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Monoclonal Antibodies ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
No Synthase ◽  
Endothelial No Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We have produced specific monoclonal antibodies (MAb) against particulate bovine aortic endothelial nitric oxide synthase. In Western blots, native and cultured bovine aortic endothelial cells as well as cultured bovine microvascular endothelial cells possess immunoreactive NO synthase. In dot blots, MAb H210 and H32 detect 1 ng and 100 pg of purified endothelial NO synthase, respectively. Both antibodies are specific to the endothelial NO synthase and do not cross-react with other known isoforms of NO synthase, namely from the brain, from cytokine/endotoxin-induced macrophages, or from cytokine/endotoxin-induced vascular smooth muscle cells. Immunohistochemical studies demonstrated the specificity of endothelial NO synthase for endothelial cells in various bovine and human tissues. Many types of endothelial cells, macrovascular, microvascular, arterial, and venous were found to possess this specific isoform of NO synthase. Electron microscopy showed the enzyme to be associated with the plasma membrane, membranes of cytoplasmic vesicles, and in the cytoplasm in human umbilical vein endothelial cells. The results demonstrate that particulate endothelial NO synthase is present in a site to act rapidly to produce NO for release into the blood or toward the smooth muscle in many vascular beds.

Profound biopterin oxidation and protein tyrosine nitration in tissues of ApoE-null mice on an atherogenic diet: contribution of inducible nitric oxide synthase

2007 ◽  
Vol 293 (5) ◽  
pp. H2878-H2887 ◽  
Author(s):  
Rita K. Upmacis ◽  
Mark J. Crabtree ◽  
Ruba S. Deeb ◽  
Hao Shen ◽  
Paul B. Lane ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Atherogenic Diet ◽  
No Synthase ◽  
Chow Diet ◽  
Tyrosine Nitration ◽  
Elevated Protein ◽  
Oxide Synthase ◽  
Lung And Kidney ◽  
Specific Contribution ◽  
Inducible Nitric Oxide

Diminished nitric oxide (NO) bioactivity and enhanced peroxynitrite formation have been implicated as major contributors to atherosclerotic vascular dysfunctions. Hallmark reactions of peroxynitrite include the accumulation of 3-nitrotyrosine (3-NT) in proteins and oxidation of the NO synthase (NOS) cofactor, tetrahydrobiopterin (BH4). The present study sought to 1) quantify the extent to which 3-NT accumulates and BH4 becomes oxidized in organs of apolipoprotein E-deficient (ApoE−/−) atherosclerotic mice and 2) determine the specific contribution of inducible NOS (iNOS) to these processes. Whereas protein 3-NT and oxidized BH4 were undetected or near the detection limit in heart, lung, and kidney of 3-wk-old ApoE−/− mice or ApoE−/− mice fed a regular chow diet for 24 wk, robust accumulation was evident after 24 wk on a Western (atherogenic) diet. Since 3-NT accumulation was diminished 3- to 20-fold in heart, lung, and liver in ApoE−/− mice missing iNOS, iNOS-derived species are involved in this reaction. In contrast, iNOS-derived species did not contribute to elevated protein 3-NT formation in kidney or brain. iNOS deletion also afforded marked protection against BH4 oxidation in heart, lung, and kidney of atherogenic ApoE−/− mice but not in brain or liver. These findings demonstrate that iNOS-derived species are increased during atherogenesis in ApoE−/− mice and that these species differentially contribute to protein 3-NT accumulation and BH4 oxidation in a tissue-selective manner. Since BH4 oxidation can switch the predominant NOS product from NO to superoxide, we predict that progressive NOS uncoupling is likely to drive atherogenic vascular dysfunctions.

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