Heme oxygenase induction attenuates afferent arteriolar autoregulatory responses

Botros, Fady T.; Prieto-Carrasquero, Minolfa C.; Martin, Victoria L.; Navar, L. Gabriel

doi:10.1152/ajprenal.90377.2008

Cited by 11 publications

(15 citation statements)

References 47 publications

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“…CO has been shown to promote relaxation of vascular smooth muscle (7), but can also cause endothelium-dependent vasoconstriction (11, 12) through inhibition of nitric oxide synthase (NOS) (13). Renal vascular resistance responses to CO have been variable ranging from a biphasic response (31) to NOS-dependent vasoconstriction (24) and direct vasodilation (4).The renal vasculature and tubules express HO (1,5,10,18,31), and treatment of rats with HO inhibitors has been reported to decrease renal blood flow (RBF) (2, 26). However, other investigators found that HO inhibition had no effect on basal renal hemodynamics (23).…”

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confidence: 99%

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Inhibition of heme oxygenase augments tubular sodium reabsorption

Jackson

Quadri³

et al. 2011

American Journal of Physiology-Renal Physiology

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Jackson KE, Jackson DW, Quadri S, Reitzell MJ, Navar LG. Inhibition of heme oxygenase augments tubular sodium reabsorption. Am J Physiol Renal Physiol 300: F941-F946, 2011. First published February 2, 2011 doi:10.1152/ajprenal.00024.2010.-Heme oxygenase (HO) catalyzes the degradation of heme to form iron, biliverdin, and carbon monoxide (CO). The vascular actions of CO include direct vasodilation of vascular smooth muscle and indirect vasoconstriction through inhibition of nitric oxide synthase (NOS). This study was performed to examine the effects in the kidney of inhibition of heme oxygenase alone or combined with NOS inhibition. Chromium mesoporphyrin (CrMP; 45 mol/kg ip), a photostable HO inhibitor, was given to control rats and N G -nitro-L-arginine methyl ester (L-NAME)-treated hypertensive rats (50 mg·kg Ϫ1 ·day Ϫ1 , 12 h, 4 days). In control animals, CrMP decreased CO levels, renal HO-1 levels, urine volume, and sodium excretion, but had no effect on arterial pressure, renal blood flow (RBF), plasma renin activity (PRA), or glomerular filtration rate (GFR). In L-NAME-treated hypertensive rats, CrMP decreased endogenous CO and renal HO-1 levels and had no effect on arterial pressure, RBF, or GFR but decreased sodium and water excretion in a similar manner to control animals. An increase in PRA was observed in untreated rats but not in L-NAME-infused rats, indicating that this effect is associated with an absent NO system. The results suggest that inhibition of HO promotes water and sodium excretion by a direct tubular action that is independent of renal hemodynamics or the NO system. renal hemodynamics; natriuresis; renal blood flow; plasma renin activity THE UBIQUITOUS ENZYME HEME oxygenase (HO) catalyzes the enzymatic degradation of heme to free iron, biliverdin, and carbon monoxide (CO) (20, 32). Two major isoforms of HO, the inducible HO-1 and the constitutive HO-2, are currently recognized (20). HO-1 is induced by a variety of stimuli, such as ischemia, hypoxia, oxidative stress, inflammation, and hypertension, while HO-2 is constitutively present. These isoforms are present in the renal vasculature, as well as in other vascular beds (2,8,14,17,32). HO activity is partly regulated by substrate availability, thus both isoforms can increase endogenous CO levels (9, 11). Pharmacological manipulation of HO has been shown to selectively influence blood flow systemically and in the kidney (18). In addition, manipulation of HO activity alters tissue CO concentrations (34).There is abundant evidence indicating that CO plays an important dual role in regulating normal vascular tone (13,14,16). CO has been shown to promote relaxation of vascular smooth muscle (7), but can also cause endothelium-dependent vasoconstriction (11, 12) through inhibition of nitric oxide synthase (NOS) (13). Renal vascular resistance responses to CO have been variable ranging from a biphasic response (31) to NOS-dependent vasoconstriction (24) and direct vasodilation (4).The renal vasculature and tubules express HO (1,5,10,18,31), a...

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confidence: 99%

“…The renal vasculature and tubules express HO (1,5,10,18,31), and treatment of rats with HO inhibitors has been reported to decrease renal blood flow (RBF) (2, 26). However, other investigators found that HO inhibition had no effect on basal renal hemodynamics (23).…”

mentioning

confidence: 99%

Inhibition of heme oxygenase augments tubular sodium reabsorption

Jackson

Quadri³

et al. 2011

American Journal of Physiology-Renal Physiology

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“…The formed biliverdin is rapidly and stereospecifically reduced to bilirubin by biliverdin reductase (17). Both biliverdin and bilirubin are antioxidants and do not seem to be involved in vascular tone regulation, as also confirmed by Botros et al (3).…”

Section: Submitted 16 July 2008; Accepted In Final Form 1 August 2008mentioning

confidence: 54%

“…To solve this issue, preparations were obtained following treatment with the two by-products of HO activity: carbon monoxide (CO) and biliverdin. In this set of experiments, Botros et al (3) showed that biliverdin failed to modify Aff-Art autoregulatory responses, whereas superfusing with 1 mmol/l CO results in a significant attenuation of autoregulatory responses to RPP increase (Fig. 1).…”

Section: Submitted 16 July 2008; Accepted In Final Form 1 August 2008mentioning

confidence: 74%

“…(3) provides evidence that induction of renal heme oxygenase-1 (HO-1) attenuates afferent arterioles (Aff-Art) constrictor responses to increased renal perfusion pressure (RPP), thus suggesting that increased HO-1 modulates renal autoregulation in pathophysiological conditions. The authors elegantly made their conclusions by first showing the HO-1 pattern distribution following heme or SnCl 2 treatment.…”

Section: Submitted 16 July 2008; Accepted In Final Form 1 August 2008mentioning

confidence: 99%

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Carbon monoxide: vasoconstrictor or vasodilator? That's the question

Volti¹,

Vanella²,

Gazzolo³

et al. 2008

American Journal of Physiology-Renal Physiology

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A STUDY BY BOTROS ET AL. (3) provides evidence that induction of renal heme oxygenase-1 (HO-1) attenuates afferent arterioles (Aff-Art) constrictor responses to increased renal perfusion pressure (RPP), thus suggesting that increased HO-1 modulates renal autoregulation in pathophysiological conditions. The authors elegantly made their conclusions by first showing the HO-1 pattern distribution following heme or SnCl 2 treatment. In particular, the authors demonstrated that in hemin-treated rats HO-1 was expressed in tubular epithelial cells with prominent staining of proximal tubules, whereas in SnCl 2 -treated rats HO-1 was detected in medullary tubular epithelial cells and few proximal tubular cells. Interestingly, HO-1 was not detected in interlobular arteries or Aff-Art following heme or SnCl 2 treatment (Fig. 1). This first set of experiments is consistent with previous studies suggesting the possibility of pharmacologically regulating HO-1 expression and HO activity in a site-specific manner along different nephron segments (1, 18). The authors then examined the physiological significance of such upregulation on Aff-Art constrictor responses to increased RPP. This evidence is of great physiological significance since this strategy has been employed to regulate vascular response in different pathological models such as hypertension (4) or diabetes (6). Additional evidence was provided by more sophisticated experiments employing HO-1 gene transfer by viral agents driven by specific promoters (15). The authors further confirmed this hypothesis showing that HO inhibition by its competitive inhibitor CrMP reversed the effects of heme and SnCl 2 (Fig. 1). This observation led the authors to hypothesize that pharmacological upregulation of HO activity could somehow be related to Aff-Art constrictor responses. To solve this issue, preparations were obtained following treatment with the two by-products of HO activity: carbon monoxide (CO) and biliverdin. In this set of experiments, Botros et al. (3) showed that biliverdin failed to modify Aff-Art autoregulatory responses, whereas superfusing with 1 mmol/l CO results in a significant attenuation of autoregulatory responses to RPP increase (Fig. 1).To better comprehend the authors' conclusions and point out the importance of the present work, one must examine the heme-HO system and its role in the regulation of key elements involved in vascular tone regulation (Fig. 2). Heme is the prosthetic group of numerous enzymes involved in this function, such as soluble guanylate cyclase (sGC) (5), nitric oxide synthase (NOS) (21), cytochrome P-450 (2) and cyclooxygenases (COX) (12). HO is the rate-limiting step in heme degradation, which leads to the formation of CO, biliverdin, and iron. HO exists as the isoenzymes HO-1 (inducible form) and HO-2 (constitutive form) (17). It is well documented that HO-1 is markedly induced by its substrate heme and by heavy metals (17). This fact, in conjunction with the robust ability of HO-1 to regulate blood pressure (18), has stimulated re...

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Involvement of endothelial-derived relaxing factors in the regulation of cerebral blood flow

Hang

Zhu

et al. 2011

Neurol Sci

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Despite numerous researches and advances in the present times, delayed cerebral vasospasm remains a severe complication leading to a high mortality and morbidity in patients with subarachnoid hemorrhage (SAH). Since the discovery of endothelium-derived relaxing factor (EDRF) in 1980, its role in delayed cerebral vasospasm after SAH has been widely investigated as well as in regulation of basic cerebral blood flow, pathophysiology of vasoconstriction and application on prevention and treatment of cerebral vasospasm. Among all the EDRFs, nitric oxide has caught the most attention, and the other substances which display similar properties with characteristics of EDRF such as carbon monoxide (CO), hydrogen sulfide (H(2)S), hydrogen peroxide (H(2)O(2)), potassium ion (K(+)) and methane (CH(4)) have also evoked great interest in the research field. This review provides an overview of recent advances in investigations on the involvement of EDRFs in the regulation of cerebral blood flow, especially in cerebral vasospasm after SAH. Possible therapeutic measures and potential clinical implications for cerebral vasospasm are also summarized.

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Heme oxygenase induction attenuates afferent arteriolar autoregulatory responses

Cited by 11 publications

References 47 publications

Inhibition of heme oxygenase augments tubular sodium reabsorption

Inhibition of heme oxygenase augments tubular sodium reabsorption

Carbon monoxide: vasoconstrictor or vasodilator? That's the question

Involvement of endothelial-derived relaxing factors in the regulation of cerebral blood flow

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