Role of CO in attenuated vasoconstrictor reactivity of mesenteric resistance arteries after chronic hypoxia

2002 ◽  
Vol 282 (1) ◽  
pp. H30-H37 ◽  
Author(s):  
Rayna J. Gonzales ◽  
Benjimen R. Walker
Keyword(s):  
Chronic Hypoxia ◽  
Protoporphyrin Ix ◽  
Aortic Ring ◽  
Mesenteric Arteries ◽  
Zinc Protoporphyrin ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Sprague Dawley Rats ◽  
Oxide Synthase

Chronic hypoxia (CH) is associated with a persistent reduction in systemic vasoconstrictor reactivity. Experiments on aortic ring segments isolated from CH rats suggest that enhanced vascular expression of heme oxygenase (HO) and resultant production of the vasodilator carbon monoxide (CO) may underlie this attenuated vasoreactivity after hypoxia. Similar to the aorta, small arteries from CH rats exhibit blunted reactivity; however, the regulatory role of CO in the resistance vasculature has not been established. Therefore, we examined the significance of HO activity on responsiveness to phenylephrine (PE) in the mesenteric circulation of control and CH rats. To document that the mesenteric bed demonstrates reduced reactivity after CH, we determined the vasoconstrictor responses of conscious, chronically instrumented male Sprague-Dawley rats to PE under control conditions and then immediately after exposure to 48 h CH (0.5 atm). All rats showed reduced mesenteric vasoconstriction to PE after CH. To examine the role of CO in reduced reactivity, small mesenteric arteries (100–200 μm intraluminal diameter) from control and 48-h CH rats were isolated and mounted on glass cannulas, pressurized to 60 mmHg and superfused with increasing concentrations of PE under normoxic conditions. Similar to the intact circulation, vessels from CH rats exhibited reduced vasoconstrictor sensitivity to PE compared with controls that persisted in the presence of nitric oxide synthase inhibition. The HO inhibitor, zinc protoporphyrin IX (5 μM) enhanced reactivity only in CH vessels. Additionally, a range of concentrations of the HO substrate heme-l-lysinate caused vasodilation in CH vessels but not in controls. Thus we conclude that CO contributes a significant vasodilator influence in resistance vessels after CH that may account for diminished vasoconstrictor responsiveness under these conditions.

scholarly journals Augmented central nitric oxide production inhibits vasopressin release during hemorrhage in acute alcohol-intoxicated rodents

2011 ◽  
Vol 301 (5) ◽  
pp. R1529-R1539 ◽  
Author(s):  
Annie M. Whitaker ◽  
Jesse K. Sulzer ◽  
Patricia E. Molina
Keyword(s):  
Nitric Oxide ◽  
Alcohol Intoxication ◽  
Sprague Dawley ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vasopressin Release ◽  
No Inhibition ◽  
Sprague Dawley Rats ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Acute alcohol intoxication (AAI) attenuates the AVP response to hemorrhage, contributing to impaired hemodynamic counter-regulation. This can be restored by central cholinergic stimulation, implicating disrupted signaling regulating AVP release. AVP is released in response to hemorrhage and hyperosmolality. Studies have demonstrated nitric oxide (NO) to play an inhibitory role on AVP release. AAI has been shown to increase NO content in the paraventricular nucleus. We hypothesized that the attenuated AVP response to hemorrhage during AAI is the result of increased central NO inhibition. In addition, we predicted that the increased NO tone during AAI would impair the AVP response to hyperosmolality. Conscious male Sprague-Dawley rats (300–325 g) received a 15-h intragastric infusion of alcohol (2.5 g/kg + 300 mg·kg−1·h−1) or dextrose prior to a 60-min fixed-pressure hemorrhage (∼40 mmHg) or 5% hypertonic saline infusion (0.05 ml·kg−1·min−1). AAI attenuated the AVP response to hemorrhage, which was associated with increased paraventricular NO content. In contrast, AAI did not impair the AVP response to hyperosmolality. This was accompanied by decreased paraventricular NO content. To confirm the role of NO in the alcohol-induced inhibition of AVP release during hemorrhage, the nitric oxide synthase inhibitor, nitro-l-arginine methyl ester (l-NAME; 250 μg/5 μl), was administered centrally prior to hemorrhage. l-NAME did not further increase AVP levels during hemorrhage in dextrose-treated animals; however, it restored the AVP response during AAI. These results indicate that AAI impairs the AVP response to hemorrhage, while not affecting the response to hyperosmolality. Furthermore, these data demonstrate that the attenuated AVP response to hemorrhage is the result of augmented central NO inhibition.

Resistance artery vasodilation to magnesium sulfate during pregnancy and the postpartum state

2005 ◽  
Vol 288 (4) ◽  
pp. H1521-H1525 ◽  
Author(s):  
Anna G. Euser ◽  
Marilyn J. Cipolla
Keyword(s):  
Magnesium Sulfate ◽  
Systemic Blood Pressure ◽  
Mesenteric Arteries ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Buffer Solution ◽  
Sprague Dawley Rats ◽  
Small Resistance ◽  
Vascular Beds ◽  
Hepes Buffer Solution

This study compared the vasodilatory responses to magnesium sulfate (MgSO4) of cerebral and mesenteric resistance arteries and determined whether the responses varied between different gestational groups. Third-order branches (<200 μm) of the posterior cerebral (PCA) and mesenteric arteries (MA) were dissected from nonpregnant (NP; n = 6), late pregnant (LP; day 19, n = 6), and postpartum (PP; day 3, n = 6) Sprague-Dawley rats. A concentration-response curve was performed by replacing the low-MgSO4 (1.2 mM) HEPES buffer solution with increasing concentrations of MgSO4 (4, 6, 8, 16, and 32 mM) and measuring lumen diameter at each concentration. All groups exhibited concentration-dependent dilation to MgSO4, decreasing the amount of tone in the vessels. However, MA were significantly more sensitive to MgSO4 than PCA. Whereas there was no difference in the response between different gestational groups in MA, the PCA from the LP and PP groups showed a significantly diminished response to MgSO4. The percent dilation at 32 mM MgSO4 for PCA versus MA in NP, LP, and PP animals was 36 ± 2 vs. 51 ± 7% ( P < 0.05), 19 ± 9 vs. 54 ± 6% ( P < 0.01 vs. PCA and NP), and 12 ± 5 vs. 52 ± 11% ( P < 0.01 vs. PCA and NP). These results demonstrate that MgSO4 is a vasodilator of small resistance arteries in the cerebral and mesenteric vascular beds. The refractory responses of the PCA in LP and PP groups demonstrate changes in the cerebrovascular vasodilatory mechanisms with gestation. The greater sensitivity of the MA to MgSO4-induced vasodilation suggests that the prophylactic effect of MgSO4 on eclamptic seizures may be more closely related to the lowering of systemic blood pressure than to an effect on cerebral blood flow.

Regional variation in resistance artery diameter responses to alpha-adrenergic stimulation during pregnancy

1993 ◽  
Vol 264 (1) ◽  
pp. H78-H85 ◽  
Author(s):  
G. D'Angelo ◽  
G. Osol
Keyword(s):  
Regional Variation ◽  
Mesenteric Arteries ◽  
Lumen Diameter ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Adrenergic Stimulation ◽  
Uterine Arteries ◽  
Sprague Dawley Rats ◽  
Pressor Responses ◽  
Pregnant State

Whole animal pressor responses are blunted during pregnancy; yet, uterine arteries, paradoxically, become significantly more sensitive to the constrictor effects of phenylephrine (PE). The objectives herein were to investigate 1) the regional variation (uterine vs. mesenteric arteries) in dose-lumen diameter relationship to alpha-adrenergic stimulation during pregnancy, and 2) the selectivity of these sensitivity shifts for this pathway (PE vs. KCl). Lumen diameter was measured in isolated, pressurized (50 mmHg) arterial segments from age-matched virgin (nonpregnant; NP) and late pregnant (LP; days 19-20) Sprague-Dawley rats. Uterine arcuate vs. mesenteric arteries from NP rats were equally sensitive to either vasoconstrictor. Arcuate arteries from LP rats, however, were 4.5-fold more sensitive to PE (P < 0.01) compared with those from NP controls. Furthermore, diameter curves became superimposed at [PE] > or = 0.1 microM, even though initial diameter of arcuate arteries from LP rats was significantly larger (P < 0.001). Conversely, mesenteric arteries from LP rats were three-fold less sensitive to PE (P < 0.02), and the diameter curve displayed a corresponding parallel rightward shift. Pregnancy did not affect the sensitivity to KCl depolarization in either arcuate or mesenteric arteries. The percent reduction in lumen diameter to the maximum [KCl] was significantly decreased only in arcuate arteries from LP rats (P < 0.001). Thus, during pregnancy, divergent constrictor responses specific to alpha-adrenergic stimulation occur in resistance arteries from the uterine vs. splanchnic circulations. Consequently, concentrations of PE that are subthreshold in NP uterine arteries can elicit large changes in lumen diameter and thereby have a pronounced effect on uterine vascular resistance in the pregnant state.

Heme Oxygenase-1/Carbon Monoxide-regulated Mitochondrial Dynamic Equilibrium Contributes to the Attenuation of Endotoxin-induced Acute Lung Injury in Rats and in Lipopolysaccharide-activated Macrophages

2016 ◽  
Vol 125 (6) ◽  
pp. 1190-1201 ◽  
Author(s):  
Jianbo Yu ◽  
Jia Shi ◽  
Dan Wang ◽  
Shuan Dong ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Carbon Monoxide ◽  
Lung Injury ◽  
Mitochondrial Dynamics ◽  
Protoporphyrin Ix ◽  
Zinc Protoporphyrin ◽  
Oxygen Species ◽  
Sprague Dawley ◽  
Mitochondrial Dynamic ◽  
Sprague Dawley Rats

Abstract Background Sepsis-associated acute lung injury remains the major cause of mortality in critically ill patients and is characterized by marked oxidative stress and mitochondrial dysfunction. Mitochondrial dynamics are indispensable for functional integrity. Additionally, heme oxygenase (HO)-1/carbon monoxide conferred cytoprotection against end-organ damage during endotoxic shock. Herein, we tested the hypothesis that HO-1/carbon monoxide played a critical role in maintaining the dynamic process of mitochondrial fusion/fission to mitigate lung injury in Sprague-Dawley rats or RAW 264.7 macrophages exposed to endotoxin. Methods The production of reactive oxygen species, the respiratory control ratio (RCR), and the expressions of HO-1 and mitochondrial dynamic markers were determined in macrophages. Concurrently, alterations in the pathology of lung tissue, lipid peroxidation, and the expressions of the crucial dynamic proteins were detected in rats. Results Endotoxin caused a 31% increase in reactive oxygen species and a 41% decrease in RCR levels (n = 5 per group). In parallel, the increased expression of HO-1 was observed in lipopolysaccharide-stimulated macrophages, concomitantly with excessive mitochondrial fission. Furthermore, carbon monoxide-releasing molecule-2 or hemin normalized mitochondrial dynamics, which were abrogated by zinc protoporphyrin IX. Additionally, impaired mitochondrial dynamic balance was shown in Sprague-Dawley rats that received lipopolysaccharide, accompanied by pathologic injury, elevated malondialdehyde contents, decreased manganese superoxide dismutase activities, and lowered RCR levels in rat lung mitochondria. However, the above parameters were augmented by zinc protoporphyrin IX and were in turn reversed by hemin. Conclusions The HO-1/carbon monoxide system modulated the imbalance of the dynamic mitochondrial fusion/fission process evoked by lipopolysaccharide and efficiently ameliorated endotoxin-induced lung injury in vivo and in vitro.

Endogenous carbon monoxide is an endothelial-derived vasodilator factor in the mesenteric circulation

2003 ◽  
Vol 284 (3) ◽  
pp. H838-H845 ◽  
Author(s):  
Jay S. Naik ◽  
Theresa L. O'Donaughy ◽  
Benjimen R. Walker
Keyword(s):  
Carbon Monoxide ◽  
Cellular Localization ◽  
Vascular Reactivity ◽  
Protoporphyrin Ix ◽  
Physiological Saline ◽  
Mesenteric Arteries ◽  
Zinc Protoporphyrin ◽  
Sprague Dawley ◽  
Vasodilator Response ◽  
Enhanced Production

Chronic hypoxia (CH) is associated with both blunted agonist-induced and myogenic vascular reactivity, possibly due to an enhanced production of heme oxygenase (HO)-derived carbon monoxide (CO). However, the cellular location of the HO responsible for these effects has not been clearly established. Therefore, we examined the response to administration of the substrate for HO, heme-l-lysinate (HLL), in endothelium-intact and endothelium-denuded small mesenteric arteries from CH male Sprague-Dawley rats. Mesenteric arteries were isolated and mounted on glass cannulas, pressurized to 60 mmHg, and superfused with physiological saline solution. All experiments were performed in the presence of 100 μM N ω-nitro-l-arginine. The vasodilator response to HLL or exogenous CO was examined. HLL experiments were performed in the presence and absence of the HO inhibitor zinc protoporphyrin IX (ZnPPIX). HLL administration resulted in a dose-dependent vasodilator response that was abolished in the presence of ZnPPIX or by endothelial removal. Exogenous CO produced a vasodilator response that was independent of an intact endothelium. Cellular localization of HO was verified through immunohistochemistry in sections of the gut and aorta from CH and control animals. Staining for HO-1, HO-2, and endothelial nitric oxide synthase was confined to the endothelium. Thus we conclude that CO is a product of HO located within the endothelium.

scholarly journals Carbon Monoxide, a Novel Neural Messenger, Does Not Modulate Extracellular Glutamate Concentration in Forebrain Ischemia

1996 ◽  
Vol 16 (5) ◽  
pp. 1075-1078 ◽  
Author(s):  
Shunya Takizawa ◽  
Hitoshi Fujita ◽  
Saori Ogawa ◽  
Yukito Shinohara
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Protoporphyrin Ix ◽  
Zinc Protoporphyrin ◽  
Forebrain Ischemia ◽  
Extracellular Glutamate ◽  
Glutamate Concentration ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity

We investigated the role of carbon monoxide as a neural modulator of extracellular glutamate concentration in rat hippocampus CA1 in transient forebrain ischemia by using metalloporphyrins, which block the production of carbon monoxide through the inhibition of heme oxygenase (HO) activity. Infusion of 10 and 100 μ M zinc protoporphyrin IX, which inhibits nitric oxide synthase activity as well as HO activity, significantly increased glutamate concentration compared with that on the vehicle-treated side. However, infusion of 100 μ M tin mesoporphyrin IX, which inhibits only HO activity, did not affect glutamate concentration in ischemia. Our results therefore do not support the hypothesis that carbon monoxide acts as a neural messenger through the modulation of extracellular glutamate concentration in ischemia.

Functional NOS 1 in the rat mesenteric arterial bed

2002 ◽  
Vol 283 (2) ◽  
pp. H658-H663 ◽  
Author(s):  
Jennifer C. Sullivan ◽  
Ararat D. Giulumian ◽  
David M. Pollock ◽  
Leslie C. Fuchs ◽  
Jennifer S. Pollock
Keyword(s):  
Nitric Oxide ◽  
Molecular Mass ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Sprague Dawley Rats ◽  
Lower Molecular Mass ◽  
Mesenteric Arterial Bed ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Mass Form

Previously we have demonstrated functional nitric oxide synthase (NOS) 1 in large arteries. Because resistance arteries largely determine blood pressure, this study examined whether functional NOS 1 also exists in resistance arteries. Phenylephrine (PE) contraction was measured in the absence and presence of the NOS 1 inhibitor N 5-(1-imino-3-butenyl)-l-ornithine (VNIO) in isolated mesenteric resistance arteries (endothelium intact and denuded) from Sprague-Dawley rats. For NOS 1 activity and expression, the mesenteric arterial bed was separated into cytosolic and particulate fractions. NOS activity was assayed by measuring the conversion of [3H]arginine to [3H]citrulline inhibited by a nonselective NOS inhibitor or VNIO. VNIO increased PE sensitivity in endothelium-intact and -denuded arteries. In cytosolic and particulate fractions of the arterial bed, ∼40% of NOS activity was inhibited by VNIO. Immunoprecipitation and Western blot analysis revealed two NOS 1 immunoreactive bands. One band corresponded to the rat brain isoform, whereas the second was of a slightly lower molecular mass. The cytosolic fraction contained both isoforms; however, the particulate fraction had only the lower molecular mass form. These studies demonstrate the existence of functional NOS 1 in resistance arteries.

Contribution of vasomotion to vascular resistance: a comparison of arteries from virgin and pregnant rats

1998 ◽  
Vol 85 (6) ◽  
pp. 2255-2260 ◽  
Author(s):  
Robert J. Gratton ◽  
Robin E. Gandley ◽  
John F. McCarthy ◽  
Walter K. Michaluk ◽  
Bryan K. Slinker ◽  
...  
Keyword(s):  
Vascular Resistance ◽  
Vessel Diameter ◽  
Mesenteric Arteries ◽  
Oscillatory Activity ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Adrenergic Agonist ◽  
Pregnant Rats ◽  
Sprague Dawley Rats ◽  
Vasomotor Activity

Intrinsic oscillatory activity, or vasomotion, within the microcirculation has many potential functions, including modulation of vascular resistance. Alterations in oscillatory activity during pregnancy may contribute to the marked reduction in vascular resistance. The purpose of this study was 1) to mathematically model the oscillatory changes in vessel diameter and determine the effect on vascular resistance and 2) to characterize the vasomotion in resistance arteries of pregnant and nonpregnant (virgin) rats. Mesenteric arteries were isolated from Sprague-Dawley rats and studied in a pressurized arteriograph. Mathematical modeling demonstrated that the resistance in a vessel with vasomotion was greater than that in a static vessel with the same mean radius. During constriction with the α1-adrenergic agonist phenylephrine, the amplitude of oscillation was less in the arteries from pregnant rats. We conclude that vasomotor activity may provide a mechanism to regulate vascular resistance and blood flow independent of static changes in arterial diameter. During pregnancy the decrease in vasomotor activity in resistance arteries may contribute to the reduction in peripheral vascular resistance.

scholarly journals Mild DOCA-salt hypertension: sympathetic system and role of renal nerves

2011 ◽  
Vol 300 (5) ◽  
pp. H1781-H1787 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink
Keyword(s):  
Control Period ◽  
Whole Body ◽  
Renal Nerves ◽  
Experimental Hypertension ◽  
Sympathetic Activation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Salt Hypertension ◽  
Hypertension Development

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration ( day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.

Chronic intravenous administration of V1 arginine vasopressin agonist results in sustained hypertension

1994 ◽  
Vol 267 (2) ◽  
pp. H751-H756 ◽  
Author(s):  
A. W. Cowley ◽  
E. Szczepanska-Sadowska ◽  
K. Stepniakowski ◽  
D. Mattson
Keyword(s):  
Body Weight ◽  
Arginine Vasopressin ◽  
Plasma Catecholamines ◽  
Plasma Osmolality ◽  
Sprague Dawley ◽  
Prolonged Administration ◽  
Chronic Stimulation ◽  
Sustained Hypertension ◽  
Sprague Dawley Rats

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.

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