Acute renal hemodynamic effects of dimanganese decacarbonyl and cobalt protoporphyrin

Arregui, Begoña; López, Bernardo; Salom, Miguel G.; Valero, Fernando; Navarro, Concepción; Fenoy, Francisco J.

doi:10.1111/j.1523-1755.2004.00409.x

Cited by 63 publications

(41 citation statements)

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“…In prior studies, inhibition of HO activity decreases GFR and/or renal blood flow in vehicle-treated rats with intact kidneys and not concomitantly exposed to vasoactive agents (5,33,45). The basis for these differing effects is uncertain at the present time.…”

Section: Discussionmentioning

confidence: 97%

Heme oxygenase activity as a determinant of the renal hemodynamic response to low-dose ANG II

Nath

Hernandez

Croatt

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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II causes renal injury through hemodynamic and other effects, and pressor doses of ANG II induce heme oxygenase-1 (HO-1) as a protective response. The present studies examined the hemodynamic effects of more clinically relevant, lower doses of ANG II and the role of HO activity in influencing these effects. Under euvolemic conditions, ANG II increased arterial pressure and renal vascular resistance. ANG II did not induce oxidative stress, inflammation/injury-related gene expression, or proteinuria and did not alter extrarenal vascular reactivity. At these doses, ANG II failed to increase HO-1 or HO-2 mRNA expression or HO activity. Inhibiting HO activity in ANG II-treated rats by tin mesoporphyrin further increased renal vascular resistances, decreased renal blood flow, and blunted the rise in arterial pressure without inducing oxidative stress or altering expression of selected vasoactive/ injury/inflammation-related genes; tin mesoporphyrin did not alter vasorelaxation of mesenteric resistor vessels. We conclude that in this model renal vasoconstriction occurs without the recognized adverse effects of ANG II on glomerular filtration rate, renal blood flow, oxidative stress, vascular reactivity, proteinuria, and injury-related gene expression; renal HO activity is essential in preserving perfusion of the ANG II-exposed kidney. These findings represent an uncommon example wherein function of a stressed organ (by ANG II), but not that of the unstressed organ, requires intact renal HO activity, even when the imposed stress neither induces HO-1 nor HO activity. These findings may be germane to conditions attended by heightened ANG II levels, ineffective renal perfusion, and susceptibility to acute kidney injury. tin mesoporphyrin; ischemia ANG II IS A MAJOR CONTRIBUTOR to chronic kidney disease by virtue of its hemodynamic, proinflammatory, and profibrotic effects. Indeed, agents that interrupt the generation of ANG II and the engagement of ANG II with its receptor comprise a fundamental therapeutic approach in the management of patients with chronic kidney disease (12,20,22). Such therapies, however, reduce but do not abort the progression of chronic kidney disease, and thus complementary strategies that can synergize with these therapies would be of interest. In this regard, a fundamental basis for the injurious effects of ANG II involves the imposition of oxidant stress via NADPH oxidase (35). Studies by us and others have demonstrated that ANG II induces the antioxidant gene heme oxygenase-1 (HO-1) (3, 4, 11) in the kidney in vivo and in vitro and that such induction of HO-1, by virtue of its antioxidant, anti-inflammatory, and vasorelaxant properties (1,2,15,24), is implicated as an adaptive, protective mechanism that can reduce the severity of ANG II-induced renal injury.An established approach employed in studying the pathogenetic basis for ANG II-induced renal injury utilizes the chronic administration of ANG II by osmotic minipumps. Such studies demonstrate that ANG II, so administered, provokes markedly i...

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Section: Discussionmentioning

confidence: 97%

Heme oxygenase activity as a determinant of the renal hemodynamic response to low-dose ANG II

Nath

Hernandez

Croatt

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…These experiments were performed as described above, except that a thermocouple (0.5 mm diameter) was inserted into the renal cortex, to allow for the measurement of renal temperature during renal artery occlusion. We found that a continuous dripping of warm saline maintains renal temperature during reductions of renal blood flow (1) or during renal artery occlusion.…”

Section: Methodsmentioning

confidence: 94%

“…A tracheotomy was performed, allowing the animals to breath spontaneously, and cannulas were placed in the jugular vein for infusions and in the right femoral artery for measurement of mean arterial pressure. The left kidney was immobilized in a plastic holder (1,17,18) and maintained warm by a continuous dripping of saline at 37°C, as it is done in micropuncture experiments (6,7). Because electrochemical NO measurements can be affected by changes in temperature, the effects of renal artery occlusion on renal temperature were evaluated in previous experiments as described (1).…”

Section: Methodsmentioning

confidence: 99%

“…The left kidney was immobilized in a plastic holder (1,17,18) and maintained warm by a continuous dripping of saline at 37°C, as it is done in micropuncture experiments (6,7). Because electrochemical NO measurements can be affected by changes in temperature, the effects of renal artery occlusion on renal temperature were evaluated in previous experiments as described (1). These experiments were performed as described above, except that a thermocouple (0.5 mm diameter) was inserted into the renal cortex, to allow for the measurement of renal temperature during renal artery occlusion.…”

Section: Methodsmentioning

confidence: 99%

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Renal ischemia induces an increase in nitric oxide levels from tissue stores

Salom

Arregui²,

Carbonell³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Tissue nitric oxide (NO) levels increase dramatically during ischemia, an effect that has been shown to be partially independent from NO synthases. Because NO is stored in tissues as S-nitrosothiols and because these compounds could release NO during ischemia, we evaluated the effects of buthionine sulfoximine (BSO; an intracellular glutathione depletor), light stimulation (which releases NO, decomposing S-nitrosothiols), and N-acetyl-L-cysteine (a sulfhydryl group donor that repletes S-nitrosothiols stores) on the changes in outer medullary NO concentration produced during 45 min of renal artery occlusion in anesthetized rats. Renal ischemia increased renal tissue NO concentration (ϩ223%), and this effect was maintained along 45 min of renal arterial blockade. After reperfusion, NO concentration fell below preischemic values and remained stable for the remainder of the experiment. Pretreatment with 10 mg/kg nitro-L-arginine methyl ester (L-NAME) decreased significantly basal NO concentration before ischemia, but it did not modify the rise in NO levels observed during ischemia. In rats pretreated with 4 mmol/kg BSO and L-NAME, ischemia was followed by a transient increase in renal NO concentration that fell to preischemic values 20 min before reperfusion. A similar response was observed when the kidney was illuminated 40 min before the ischemia. The coadministration of 10 mg/kg iv N-acetyl-L-cysteine with BSO ϩ L-NAME restored the increase in NO levels observed during renal ischemia and prevented the depletion of renal thiol groups. These results demonstrate that the increase in renal NO concentration observed during ischemia originates from thiol-dependent tissue stores. voltammetry; nitrosothiols; N-acetyl-L-cysteine; buthionine sulfoximine; photosensitive nitric oxide release IT HAS BEEN REPORTED THAT arterial ischemia produces an abrupt and significant increase in tissue nitric oxide (NO) concentration, which can last as long as ischemia is maintained and returns to preischemic levels during reperfusion. This phenomenon has been observed in kidney (27), liver (16), heart (40), gastric tissue (15), and brain (39); although its physiological relevance is unclear, it may generate the high levels of peroxynitrite anion formed during reperfusion when a burst of superoxide anion reacts with the high levels of NO accumulated during ischemia (21), thus contributing to reperfusion damage. The mechanism responsible for these increased NO levels during renal ischemia is unknown, although it seems to be partially insensitive to NO synthesis inhibition, at least in liver and kidney (16,27). This is not surprising because NO synthase (NOS) requires molecular oxygen. Therefore, during ischemia, NO must be released from other sources, such as tissue NO stores (22,26,31).In the presence of oxygen, NO is synthesized from Larginine through the action of NOS, and this gaseous hormone acts in the kidney by stimulating guanylyl cyclase and by inhibiting cytochrome P-450 (18). However, as soon as it is synthesized, NO avidly react...

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“…[52][53][54] In the kidney, studies using specific CORMs have found that increases in CO produce increases in renal blood flow that are significantly but not totally reduced by blockade of sGC and completely blocked by inhibition of K ϩ channels. 55,56 CO provides an important counterbalance against vasoconstriction mediated by such agents as Ang II and 20-hydroxyeciosatetrenoic acid, especially in the renal vasculature. 54,57 CO, derived from either endothelial or smoothmuscle HO, can directly inactivate P450 enzymes in the vasculature by binding to the heme moiety in the enzyme.…”

Section: Co and The Vasculature: Does The Goodmentioning

confidence: 99%

Role of Carbon Monoxide in Blood Pressure Regulation

2008

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C arbon monoxide (CO) is an odorless, colorless, tasteless gas that is generated in the environment as the result of combustion from stoves and engines among other sources. Approximately 500 people per year in the United States are victims of nonfire-associated CO poisoning according to the Centers for Disease Control and Prevention. CO poisoning is often fatal because of its interaction with hemoglobin, which renders it incapable of carrying oxygen-causing organs to become severely hypoxic. CO inhalation is believed to be fatally toxic at concentrations as little as 800 parts per million (ppm) or 0.08% in the air. Despite the lethal nature of this gas, several recent studies suggest that CO inhalation at low doses (Յ250 ppm), as well as increases in CO levels using CO releasing molecules (CORMs), offers protection against ischemic injury in the heart, liver, and kidney. [1][2][3][4] CO is endogenously produced in the body as a result of the metabolism of heme by heme oxygenase (HO), as well as from lipid peroxidation. 5,6 The catabolism of heme by HO also produces an equimolar amount of biliverdin, which is rapidly converted in the cell to bilirubin by the enzyme biliverdin reductase. 7 There are 2 major isoforms of HO responsible for CO production. HO-1 is expressed at very low levels under normal conditions but is highly induced by several stimuli, including heavy metals, ultraviolet light, endotoxin, shear stress, hypoxia, and oxidants. 8 HO-2 is the constitutively expressed form of the enzyme with the highest levels observed in the brain and testes. 9 Experimental evidence has demonstrated that systemic induction of HO has several beneficial actions on the cardiovascular system, including lowering of blood pressure, protection against myocardial infarction, and prevention of atherosclerosis. 10 -12 Although the cardiovascular actions of HO induction have been established, the role of CO in mediating these responses is not clear. The purpose of this review is to outline the potential antihypertensive actions of CO and highlight areas that may pose new opportunities for the development of novel therapeutic targets for the treatment of hypertension. Altering CO Levels In Vivo: Tools of the TradeThere are 3 main approaches that have been used to alter tissue levels of CO in vivo, which need to be briefly discussed. These include inhibition/induction of HO, CO inhalation, and CORMs. Each of these approaches has its own advantages and limitations depending on the specific experimental settings in which tissue levels of CO are to be altered. HO induction/inhibition has been widely used because of the fact that most of the endogenous CO produced in vivo is derived from HO. Given the routine ability to alter HO in a tissue-and temporal-specific fashion either pharmacologically or genetically, this is an attractive option for examining CO in vivo. However, there are several limitations in altering HO levels to examine the role of CO in vivo. First among these is the specificity of the majority of the metalloporphyr...

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Acute renal hemodynamic effects of dimanganese decacarbonyl and cobalt protoporphyrin

Abstract: These results indicate that heme oxygenase-derived CO plays a cardinal role in the control of renal hemodynamics and glomerular filtration.

Cited by 63 publications

References 47 publications

Heme oxygenase activity as a determinant of the renal hemodynamic response to low-dose ANG II

Heme oxygenase activity as a determinant of the renal hemodynamic response to low-dose ANG II

Renal ischemia induces an increase in nitric oxide levels from tissue stores

Role of Carbon Monoxide in Blood Pressure Regulation

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