Carbon monoxide produced by isolated arterioles attenuates pressure-induced vasoconstriction

Zhang, Fan; Kaide, Jun-Ichi; Wei, Yuan; Jiang, Houli; Yu, Chenxu; Balazy, Michael; Abraham, Nader G.; Wang, Wenhui; Nasjletti, Alberto

doi:10.1152/ajpheart.2001.281.1.h350

Cited by 76 publications

(67 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 CO-induced dilations are inhibited by blockers of the large-conductance Ca 2ϩ -activated K ϩ (K Ca ) channel in tail, gracilis muscle, renal, and cerebral arteries. 3,[35][36][37] These findings support an important role for K Ca channels in CO dilations. It has been shown that adenosine stimulated the increase of intracellular Ca 2ϩ concentration and mobilized cytosolic Ca 2ϩ of neurons.…”

Section: Discussionsupporting

confidence: 63%

Interaction of Carbon Monoxide and Adenosine in the Nucleus Tractus Solitarii of Rats

Lin

Hsiao

et al. 2003

Hypertension

View full text Add to dashboard Cite

Abstract-Carbon monoxide has been identified as an endogenous biological messenger in the brain. Heme oxygenase catalyzes the metabolism of heme to carbon monoxide and biliverdin. Previously, we have shown the involvement of carbon monoxide in central cardiovascular regulation, baroreflex modulation, and glutamatergic neurotransmission in the nucleus tractus solitarii of rats. We also showed that adenosine increased the release of glutamate in the nucleus tractus solitarii. In this study, we investigated the possible interactions of carbon monoxide and adenosine in the nucleus tractus solitarii. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure were monitored intra-arterially. Unilateral microinjection of increasing doses of hemin (0.01 to 3.3 nmol), a heme molecule cleaved by heme oxygenase to yield carbon monoxide, produced a significant decrease in blood pressure and heart rate in a dose-dependent manner. In addition, similar cardiovascular effects were observed after injection of adenosine (2.3 nmol). These cardiovascular effects of hemin were attenuated by prior administration of the adenosine receptor antagonist 1,3-dipropyl-8-sulfophenylxanthine. Similarly, pretreatment of the heme oxygenase inhibitor zinc protoporphyrin IX or zinc deuteroporphyrin 2,4-bis glycol also attenuated the depressor and bradycardic effects of adenosine.These results indicate that the interaction between carbon monoxide and adenosine may contribute to the activation of heme oxygenase in central cardiovascular regulation. Key Words: central nervous system Ⅲ blood pressure Ⅲ adenosine Ⅲ heart rate Ⅲ neuroregulators T he gaseous compound carbon monoxide (CO), a new neuromodulator agent, has been shown to play a role as a neurotransmitter. 1 In animals, the predominant source of CO generation is from heme degradation. Heme oxygenase (HO) is the rate-limiting enzyme responsible for the catabolism of heme and subsequent production of CO and biliverdin. Three isoforms of HO have been identified. HO-1, induced by heme and numerous oxidative stressors, is enriched in spleen and liver. HO-2 is present abundantly in the brain and testis as a constitutive enzyme. HO-3 has been identified in brain, heart, kidney, liver, testis, and spleen. 1 Studies have suggested that CO arising from heme through metabolism by HO stimulates soluble guanylate cyclase (sGC) activity and promotes an increase in cGMP in neural and cardiovascular tissues. [2][3][4] These results implicate the HO/CO system as a potential regulator of various neural and cardiovascular functions.HO is widely expressed in the brain and is responsible for the CO-generating ability of the brain, including brain stem. 2,5 In the central nervous system (CNS), the nucleus of the solitary tract (NTS) is the site where afferent fibers arising from arterial baroreceptor, chemoreceptors, cardiopulmonary receptors, and other visceral receptors form the first central synapses 6 and thus play an important role in the integration of autonomic control of the cardiovascul...

show abstract

Section: Discussionsupporting

confidence: 63%

Interaction of Carbon Monoxide and Adenosine in the Nucleus Tractus Solitarii of Rats

Lin

Hsiao

et al. 2003

Hypertension

View full text Add to dashboard Cite

show abstract

“…Abundances of ions at mass-to-charge ratios (m/z) of 28, 29, and 31, which correspond to 12 C 16 O, 13 C 16 O, and 13 C 18 O, respectively, were acquired via selected ion monitoring. The amount of CO in each cell-culture sample was calculated using standard curves that were constructed from ion abundances with m/z values of 28 and 29 or 31 as previously described (42).…”

Section: Methodsmentioning

confidence: 99%

Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells

Abraham

Quan²,

Mieyal³

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

and increases guanosine 3Ј,5Ј-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N -nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition. guanosine 3Ј,5Ј-cyclic monophosphate; retroviral vector; soluble guanylate cyclase; heme oxygenase CELLULAR LEVELS OF HEME are regulated by the rates of heme synthesis and degradation. Heme catabolism occurs by oxidative cleavage of the ␣-methene bridge of the tetrapyrrole, which eventually leads to the formation of equimolar amounts of biliverdin and carbon monoxide (CO) and the release of the contained iron atom. Biliverdin is then rapidly reduced to form bilirubin (3). The heme oxygenase (HO) system controls the rate-limiting step in heme catabolism (3). To date, three HO isoforms have been identified: HO-1, HO-2, and HO-3. HO-1 is a 32-kDa heat shock protein (29,34) that is inducible by numerous noxious stimuli (8,21,23,30); HO-2 is a constitutively synthesized 36-kDa protein that is abundant in the brain and testis (26,35); and HO-3 exhibits 90% homology to

show abstract

“…One microliter of the [ 13 C]carbon monoxide saturated solution (1 mM) was added to the sample, resulting in the internal standard concentration of 1 M. After sample equilibration, 100 l of the headspace gas was taken from the vial and injected into the gas chromatograph. The amount of CO in cell culture samples was calculated from standard curves constructed with abundance of ions m͞z 28 and m͞z 29 or m͞z 31 as previously described (28). Both standard curves were linear over the range 0.05-5.0 mol/liter, and both yielded comparable results when used for determining the concentration of endogenous CO (28).…”

Section: Development Of Recombinant Retroviralmentioning

confidence: 99%

“…The amount of CO in cell culture samples was calculated from standard curves constructed with abundance of ions m͞z 28 and m͞z 29 or m͞z 31 as previously described (28). Both standard curves were linear over the range 0.05-5.0 mol/liter, and both yielded comparable results when used for determining the concentration of endogenous CO (28).…”

Section: Development Of Recombinant Retroviralmentioning

confidence: 99%

Regulation of human heme oxygenase in endothelial cells by using sense and antisense retroviral constructs

Quan

Yang

Abraham

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

C ellular levels of heme are regulated by the rates of its synthesis and degradation. Heme catabolism occurs by oxidative cleavage of the ␣-methene bridge of the tetrapyrrole, eventually leading to the formation of equimolar amounts of biliverdin and CO and the release of the contained iron atom (1, 2). Biliverdin is then rapidly reduced to form bilirubin (3, 4). The heme oxygenase (HO) system controls the rate-limiting step in heme catabolism (5). To date, three HO isoforms (HO-1, HO-2, and HO-3) have been identified that catalyze this reaction (6-8). HO-1 is a 32-kDa heat shock protein (9-11) that is inducible by numerous noxious stimuli (12-17). HO-2 is a constitutively synthesized 36-kDa protein that is abundant in brain and testis (6). HO-3 is related to HO-2, but is the product of a different gene, and its ability to catalyze heme degradation is much less than that of .Overexpression of HO-1 can lead to hyperbilirubinemia in humans with certain hepatic disorders, especially patients in whom bilirubin disposition is impaired for developmental or genetic reasons, i.e., in newborns and in patients with the Crigler-Najjar type I syndrome. Pharmacological agents such as the inhibitor of HO, tin mesoporphyrin, can inhibit HO activity significantly and have been shown to be highly effective in single dose in controlling hyperbilirubinemia in newborns and other patients (19-23). However, such agents can exert only transient control of the activity of HO-1. Further, the long-term overexpression or underexpression of human HO-1 (HHO-1) would have considerable experimental value in elucidating the role of the enzyme in physiological and pathological processes.The objective of this study was to examine the feasibility of using the retrovirus-mediated transfer of an HHO-1 sense (S) and antisense (AS) orientation sequence under the control of the HHO-1 promoter to regulate endogenous HO-1 expression and function and thus permit development of a gene transfer technology to regulate the rate of heme catabolism over the long term.Our data demonstrate that selective delivery of the HHO-1 gene in AS orientation into human endothelial cells results in an attenuation of HHO-1 protein leading to a decrease in the rate of catabolism of cellular heme and that this effect is brought about without altering endogenous HO-2 protein. Thus, by the use of the retroviral HO-1 AS methodology it is possible to envisage prolonged down-regulation of the rate of heme catabolism to its degradation product bilirubin in clinical or experimental circumstances where this might prove useful. Materials and MethodsCell Culture Conditions. The amphotropic retroviral packaging cell line PA317 (American Type Culture Collection) or PT67 (CLON-TECH) was used for the generation of replication-deficient recombinant retroviruses. PA317 and PT67 cells were grown in DMEM (GIBCO͞BRL, Grand Island, NY) supplemented with 10% heatinactivated FBS. NIH 3T3 fibroblasts were cultured in DMEM with 10% calf serum. Human dermal microvessel endothelial cells (HMEC-1 cells...

show abstract

Carbon monoxide produced by isolated arterioles attenuates pressure-induced vasoconstriction

Cited by 76 publications

References 24 publications

Interaction of Carbon Monoxide and Adenosine in the Nucleus Tractus Solitarii of Rats

Interaction of Carbon Monoxide and Adenosine in the Nucleus Tractus Solitarii of Rats

Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells

Regulation of human heme oxygenase in endothelial cells by using sense and antisense retroviral constructs

Contact Info

Product

Resources

About