NO contributes to neurohypophysial but not other regional cerebral fluorocarbon-induced hyperemia in cats

Wagner, B. P.; Stingele, Robert; Williams, M. A.; Wilson, D. A.; Traystman, R. J.; Hanley, Daniel F.

doi:10.1152/ajpheart.1997.273.4.h1994

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…Blood flow results in the neurohypophysis, in which the blood vessels are highly permeable and NO exerts a tonic vasodilatory effect (37), offer a useful contrast with the rest of the brain. Whereas L-NAME decreased blood flow in both the cerebrum and neurohypophysis, Hb transfusion decreased blood flow only in neurohypophysis.…”

Section: Discussionmentioning

confidence: 99%

Role of nitric oxide scavenging in vascular response to cell-free hemoglobin transfusion

Sampei

Ulatowski²,

Asano

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Modified Hb solutions have been developed as O(2) carrier transfusion fluids, but of concern is the possibility that increased scavenging of nitric oxide (NO) within the plasma will alter vascular reactivity even if the Hb does not readily extravasate. The effect of decreasing hematocrit from approximately 30% to 18% by an exchange transfusion of a 6% sebacyl cross-linked tetrameric Hb solution on the diameter of pial arterioles possessing tight endothelial junctions was examined through a cranial window in anesthetized cats with and without a NO synthase (NOS) inhibitor. Superfusion of a NOS inhibitor decreased diameter, and subsequent Hb transfusion produced additional constriction that was not different from Hb transfusion alone but was different from the dilation observed by exchange transfusion of an albumin solution after NOS inhibition. In contrast, abluminal application of the cross-linked Hb produced constriction that was attenuated by the NOS inhibitor. Neither abluminal nor intraluminal cross-linked Hb interfered with pial arteriolar dilation to cromakalim, an activator of ATP-sensitive potassium channels. Pial vascular reactivity to hypocapnia and hypercapnia was unaffected by Hb transfusion. Microsphere-determined regional blood flow indicated selective decreases in perfusion after Hb transfusion in the kidney, small intestine, and neurohypophysis, which does not have tight endothelial junctions. Administration of a NOS inhibitor to reduce the basal level of NO available for scavenging before Hb transfusion prevented further decreases in blood flow to these regions compared with NOS inhibition alone. In contrast, blood flow to skeletal and left ventricular muscle increased, and cerebral blood flow was unchanged after Hb transfusion. This cross-linked Hb tetramer is known to appear in renal lymph but not in urine. We conclude that cell-free tetrameric Hb does not scavenge sufficient NO in the plasma space to significantly affect baseline tone in vascular beds with tight endothelial junctions but does produce substantial constriction in beds with porous endothelium. The data support increasing the molecular size of Hb by polymerization or conjugation to limit extravasation in all vascular beds to preserve normal vascular reactivity.

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Section: Discussionmentioning

confidence: 99%

Role of nitric oxide scavenging in vascular response to cell-free hemoglobin transfusion

Sampei

Ulatowski²,

Asano

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…However, NOS inhibitors do not always seem to increase myocardial oxygen consumption (42,49,68,76); the reasons for this discrepancy are not clear, although in some cases they are likely to relate to differences in the intracellular location, local concentration, permeability and K i of different inhibitors. Interestingly, no effect has been seen of NOS inhibitors on either oxygen consumption (44,69) or the redox state of cytochrome oxidase (30) in the anesthetized brain, even in the absence of potentially NO scavenging red blood cells (90).…”

Section: The Reality Of Inhibition?mentioning

confidence: 99%

Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology

Cooper¹,

Giulivi

2007

American Journal of Physiology-Cell Physiology

147

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Cooper CE, Giulivi C. Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology. Am J Physiol Cell Physiol 292: C1993-C2003, 2007. First published February 28, 2007 doi:10.1152/ajpcell.00310.2006 is an intercellular signaling molecule; among its many and varied roles are the control of blood flow and blood pressure via activation of the heme enzyme, soluble guanylate cyclase. A growing body of evidence suggests that an additional target for NO is the mitochondrial oxygen-consuming heme/copper enzyme, cytochrome c oxidase. This review describes the molecular mechanism of this interaction and the consequences for its likely physiological role. The oxygen reactive site in cytochrome oxidase contains both heme iron (a3) and copper (CuB) centers. NO inhibits cytochrome oxidase in both an oxygen-competitive (at heme a3) and oxygen-independent (at CuB) manner. Before inhibition of oxygen consumption, changes can be observed in enzyme and substrate (cytochrome c) redox state. Physiological consequences can be mediated either by direct "metabolic" effects on oxygen consumption or via indirect "signaling" effects via mitochondrial redox state changes and free radical production. The detailed kinetics suggest, but do not prove, that cytochrome oxidase can be a target for NO even under circumstances when guanylate cyclase, its primary high affinity target, is not fully activated. In vivo organ and whole body measures of NO synthase inhibition suggest a possible role for NO inhibition of cytochrome oxidase. However, a detailed mapping of NO and oxygen levels, combined with direct measures of cytochrome oxidase/NO binding, in physiology is still awaited. mitochondria; cytochrome oxidase NITRIC OXIDE (NO) is known as an intercellular messenger, synthesized in mammalian systems from arginine, NADPH, and oxygen by the NO synthase (NOS) class of enzymes (1). It has a wide range of physiological functions, most notably the control of blood pressure and blood flow (46, 63) mediated by the production of cGMP via its activation of the heme enzyme, soluble guanylate cyclase (45).Just over a decade ago, several groups demonstrated that the primary target for NO interactions with mammalian mitochondria is at the level of the oxygen-consuming enzyme, cytochrome c oxidase (15,20,73). These, and numerous subsequent studies, have demonstrated that in vitro cytochrome c oxidase is reversibly inhibited by nanomolar levels of NO. The possible cellular consequences of this effect are described in our previous paper (38). This review will instead focus on the importance of NO interactions with cytochrome oxidase at levels of organization above that of the individual cell.Two major questions arise when contemplating the possible consequences of this interaction at the tissue/organ level. First, does it occur in vivo? Second, if so, what are the physiological consequences? Whereas the detailed molecular mechanism of inhibition might appear to be of more interest to biochemists than physiologists, un...

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“…Wagner et al (1997) observed a large increase in cerebral blood flow (CBF) in the hemispheres, brain stem, cerebellum, thalamus, and white matter after fluorocarbon (FC)-exchange transfusion in cats. They have shown that l-NAME inhibits brain NOS activity in FC-perfused cats, but does not reverse FC-exchange transfusion-induced CBF [ 54 ]. Kaufmann et al (2004) [ 55 ] assessed the effect of simultaneous inhibition of eNOS and nNOS on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers and in (denervated) transplant recipients.…”

Section: Introductionmentioning

confidence: 99%

Age-dependent redox status in the brain stem of NO-deficient hypertensive rats

et al. 2017

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BackgroundThe brain stem contains important nuclei that control cardiovascular function via the sympathetic nervous system (SNS), which is strongly influenced by nitric oxide. Its biological activity is also largely determined by oxygen free radicals. Despite many experimental studies, the role of AT1R-NAD(P)H oxidase-superoxide pathway in NO-deficiency is not yet sufficiently clarified. We determined changes in free radical signaling and antioxidant and detoxification response in the brain stem of young and adult Wistar rats during chronic administration of exogenous NO inhibitors.MethodsYoung (4 weeks) and adult (10 weeks) Wistar rats were treated with 7-nitroindazole (7-NI group, 10 mg/kg/day), a specific nNOS inhibitor, with NG-nitro-L-arginine-methyl ester (L-NAME group, 50 mg/kg/day), a nonspecific NOS inhibitor, and with drinking water (Control group) during 6 weeks. Systolic blood pressure was measured by non-invasive plethysmography. Expression of genes (AT1R, AT2R, p22phox, SOD and NOS isoforms, HO-1, MDR1a, housekeeper GAPDH) was identified by real-time PCR. NOS activity was detected by conversion of [3H]-L-arginine to [3H]-L-citrulline and SOD activity was measured using UV VIS spectroscopy.ResultsWe observed a blood pressure elevation and decrease in NOS activity only after L-NAME application in both age groups. Gene expression of nNOS (youngs) and eNOS (adults) in the brain stem decreased after both inhibitors. The radical signaling pathway triggered by AT1R and p22phox was elevated in L-NAME adults, but not in young rats. Moreover, L-NAME-induced NOS inhibition increased antioxidant response, as indicated by the observed elevation of mRNA SOD3, HO-1, AT2R and MDR1a in adult rats. 7-NI did not have a significant effect on AT1R-NADPH oxidase-superoxide pathway, yet it affected antioxidant response of mRNA expression of SOD1 and stimulated total activity of SOD in young rats and mRNA expression of AT2R in adult rats.ConclusionOur results show that chronic NOS inhibition by two different NOS inhibitors has age-dependent effect on radical signaling and antioxidant/detoxificant response in Wistar rats. While 7-NI had neuroprotective effect in the brain stem of young Wistar rats, L-NAME- induced NOS inhibition evoked activation of AT1R-NAD(P)H oxidase pathway in adult Wistar rats. Triggering of the radical pathway was followed by activation of protective compensation mechanism at the gene expression level.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-017-0366-4) contains supplementary material, which is available to authorized users.

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NO contributes to neurohypophysial but not other regional cerebral fluorocarbon-induced hyperemia in cats

Cited by 5 publications

References 21 publications

Role of nitric oxide scavenging in vascular response to cell-free hemoglobin transfusion

Role of nitric oxide scavenging in vascular response to cell-free hemoglobin transfusion

Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology

Age-dependent redox status in the brain stem of NO-deficient hypertensive rats

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