Biomedical subjects

Johan Van de Voorde

Publications and source records attributed to Johan Van de Voorde.

15 recordsLinked to original sources

PubMed2006

K+ potentiates hyperosmolarity-induced vasorelaxations in rat skeletal muscle arterioles.

Several regulatory mechanisms have been proposed for the exercise hyperemia in skeletal muscles. Since different vasoactive factors might interact during the hyperemic response, we investigated the influence of elevated K(+) concentrations on hyperosmolarity (HO)-induced vasorelaxations. Small gluteal rat arteries were isolated and mounted in an organ bath for isometric tension recording. After precontraction with norepinephrine, 20 (S20), 40 (S40) or 60 mM (S60) sucrose was added in control conditions (5 mM K(+); K5) or in the presence of additional 3 (K8) or 5 mM (K10) K(+). Removal of the endothelium and the addition of ouabain, Ba(2+), iberiotoxin or 18-alpha glycyrrhetinic acid (alphaGA) were used to study the underlying mechanisms. Sucrose evoked significant concentration-dependent vasorelaxations (S20 15.62+/-1.61%; S40 26.47+/-1.71%; S60 43.66+/-2.50%), which were significantly increased on addition of 3 and 5 mM. After removal of the endothelium and in the presence of 5 x 10(-5) M alphaGA, the influence of K(+) was significantly blocked but not in the presence of 5 x 10(-5) M ouabain. The K(IR) channel inhibitor Ba(2+) and BK(Ca) channel inhibitor iberiotoxin totally abolished the potentiating effect. We conclude that K(+) significantly enhances the relaxing effect of HO in gluteal blood vessels. We hypothesize that K(+) may stimulate the endothelial K(IR) channels which elicits the release of a mediator of the BK(Ca) channels. This factor may be transferred through myo-endothelial gap-junctions to the smooth muscle cells where modulation of the BK(Ca) channels sensitizes the arteries for hyperosmolarity-induced relaxations.

Animals↗

PubMed2006

Characterization of the vasorelaxation to methanandamide in rat gastric arteries.

In the present study, the relaxant effect of the cannabinoid methanandamide was explored in rat gastric arteries. Since in some vessels cannabinoids have been shown to release calcitonin gene-related peptide (CGRP) from perivascular nerves, the influence of methanandamide was compared with that of exogenous CGRP. Methanandamide and CGRP elicited concentration-dependent, endothelium-independent relaxations. Methanandamide-induced relaxations were unaffected by the CB1 receptor antagonist AM251, the CB2 receptor antagonists AM630 and SR144528, and combined pre-exposure to AM251 and SR144528. Pre-exposure to O-1918, an antagonist of a novel nonCB1/nonCB2 cannabinoid receptor, did not influence the relaxations to methanandamide. Capsaicin or capsazepine treatment slightly inhibited methanandamide-induced relaxations. Preincubation with 30 mmol/L extracellular K+ or 3 mmol/L TEA had no significant effect on the responses elicited by methanandamide, but reduced CGRP-induced relaxations. Relaxation to 10(-5) mol/L methanandamide was significantly blunted by Bay K8644 and by preincubation with nifedipine. Furthermore, 10(-5) mol/L methanandamide significantly inhibited CaCl2-induced contractions in norepinephrine-stimulated vessels previously depleted of intra- and extracellular Ca2+. Finally, preincubation with 10(-5) mol/L methanandamide almost completely abolished high K+-induced contractions. These findings suggest that the vasorelaxant action of methanandamide in rat gastric arteries is not mediated by stimulation of known cannabinoid receptors and only partly related to stimulation of TRPV1 receptors on perivascular nerves. At high concentrations, methanandamide might induce relaxation by reducing calcium entry into the smooth muscle cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2005

Clozapine directly relaxes bovine retinal arteries.

PURPOSE: It was suggested that clozapine might be helpful in the development of new antiglaucoma agents, as it combines lowering the intraocular pressure after topical instillation with vasodilation. This study aimed to evaluate and characterize the vasodilatory effect of clozapine in isolated bovine retinal arteries (BRAs). METHODS: Retinal arteries were isolated from bovine eyes and mounted in the organ bath of a small vessel myograph. RESULTS: Cumulative addition of clozapine (1 nM to 10 microM) caused a concentration-dependent relaxation of the BRAs. Removal of the endothelium, inhibition of nitric oxide synthase and of soluble guanylyl cyclase reduced the clozapine response, whereas cyclooxygenase inhibition had no influence. A Ca2+ channel activator, a 5-hydroxytryptamine receptor antagonist, and an adenosine receptor antagonist failed in affecting the clozapine-induced relaxations. CONCLUSIONS: Clozapine relaxes bovine retinal arteries. Endothelium-derived NO seems to be involved, whereas prostanoids, calcium entry blockade, 5-HT7 receptor stimulation, and adenosine receptor stimulation do not.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2005

The vasorelaxing effect of CGRP and natriuretic peptides in isolated bovine retinal arteries.

PURPOSE: To study the vasorelaxing effect of calcitonin gene-related peptide (CGRP) and natriuretic peptides on isolated bovine retinal arteries (BRAs) and to evaluate the possibility of the unidentified retinal relaxing factor (RRF) being one of these peptides. METHODS: Retinal arteries were isolated from bovine eyes and mounted in a wire myograph for isometric tension recording. Concentration-response curves were generated by cumulative addition of the peptides to the organ bath. RESULTS: In BRAs, CGRP-induced relaxation was significantly reduced by removal of the endothelium or by application of the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-l-arginine (l-NA) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The nonselective K(+) channel blocker tetraethylammoniumchloride (TEA) and the voltage-dependent K(+) channel blocker 4-aminopyridine significantly reduced the CGRP response, whereas the Ca(2+) activated K(+) channel blockers apamin plus charybdotoxin, the inward rectifier K(+) channel blocker Ba(2+), and the adenosine triphosphate (ATP)-sensitive K(+) channel blocker glibenclamide had no effect. The CGRP receptor antagonist CGRP 8-37 caused a small, but not significant, rightward shift in the concentration-response curve for CGRP, whereas the AM-receptor antagonist AM 22-52 had no effect. The natriuretic peptides did not induce relaxation in isolated retinal arteries. CONCLUSIONS: Endothelium-derived NO, voltage-dependent K(+) channels, and possibly also CGRP(1) receptors are involved in the CGRP response in BRAs. The natriuretic peptides do not induce vasorelaxation in isolated BRAs. No evidence was found that CGRP or a natriuretic peptide is the as yet unidentified RRF.

Animals↗

PubMed2005

Vitreous: a barrier to nonviral ocular gene therapy.

PURPOSE: Intravitreal injection of therapeutic DNA, complexed to nonviral carriers such as cationic liposomes, may be promising in the treatment of many severe retinal eye diseases. However, after intravitreal injection, such DNA/cationic liposome complexes-called lipoplexes (LPXs)-which are typically hundreds of nanometers in size, must first diffuse through the vitreous before they can reach the retina. The aim of this study was to elucidate whether vitreous is a barrier for the LPXs and to find strategies to overcome this barrier. METHODS: Fluorescent polystyrene nanospheres and LPXs were mixed with vitreous, and their mobility was monitored by fluorescence recovery after photobleaching (FRAP), a microscopy-based technique. The stability of LPXs and naked plasmid DNA in vitreous was studied by gel electrophoresis. RESULTS: We showed that polystyrene nanospheres, in our first experiments used as a model for the LPXs, do not diffuse freely into the vitreous but adhere to fibrillar structures in the vitreous, most likely to collagen fibers. Making the surfaces of the polystyrene nanospheres hydrophilic by attaching hydrophilic polyethylene glycol (PEG) chains at their surfaces circumvented the binding to fibrillar structures in the vitreous. FRAP revealed that "pegylated" polystyrene nanospheres, as long as they are smaller than 500 nm, are indeed mobile in the vitreous. It was further demonstrated that LPXs severely aggregate in vitreous and strongly bind to biopolymers in the vitreous, which immobilizes them completely. However, as observed for the polystyrene nanospheres, coating of the LPXs with PEG averted their aggregation in the vitreous and their binding to fibrillar structures. CONCLUSIONS: Modifying the surfaces of LPXs with hydrophilic PEG chains prevents them from aggregating in vitreous. In this way, LPXs are obtained that can freely move in vitreous, an absolute criterion for reaching the retina after intravitreal injection.

Animals↗

PubMed2005

Hyperosmolarity causes BK Ca-dependent vasodilatations in rat skeletal muscle arteries.

PURPOSE: The release of different metabolites during skeletal muscle contraction causes a pronounced increase in extracellular osmolarity (hyperosmolarity (HO)). HO has been considered as a possible mediator of the exercise hyperemia. In the present study, we investigated the vasodilatory effect of physiologically relevant increases in the extracellular osmolarity in isolated rat gluteal muscle arterioles. In addition, we analyzed the underlying mechanisms of the HO-induced vasodilatations. METHODS: Rat gluteal arteries were isolated and mounted in an organ bath for isometric tension recording. After precontraction with norepinephrine, 20, 40, or 60 mmol x L(-1) sucrose, mannitol, or urea was added in control conditions, after removal of the endothelium or in the presence of inhibitors. RESULTS: Application of sucrose or mannitol induced large and fast concentration-dependent vasodilatations (up to 46.15% with 60 mmol x L(-1) sucrose). Removal of the vascular endothelium had no effect on this relaxation. Inhibition of the Na+/K+ pumps with ouabain, the Kir IR channels with Ba2+ and the K ATP channels with glibenclamide did not alter the HO-induced relaxations. Incubation with the KCa channel blockers charybdotoxin and apamin significantly inhibited sucrose-induced vasodilatations. In addition, application of the specific BK Ca channel blocker iberiotoxin significantly decreased the HO-induced vasodilatations. CONCLUSION: The present study shows that an increase in the extracellular osmolarity elicits strong, fast, and long-lasting relaxations of rat skeletal muscle arterioles, suggesting an important role both at the onset and during the steady-state phase of an exercise bout. Vascular smooth muscle BK Ca channels seem to play a crucial role in the HO-induced vasorelaxations.

Animals↗

PubMed2004

Endothelium-derived hyperpolarizing factor-mediated renal vasodilatory response is impaired during acute and chronic hyperhomocysteinemia.

BACKGROUND: Endothelial dysfunction is an early event in the development of vascular complications in hyperhomocysteinemia. Endothelial cells release a number of vasodilators, including NO and prostacyclin. Several lines of evidence have indicated the existence of a third vasodilator pathway, mediated by endothelium-derived hyperpolarizing factor (EDHF). EDHF is a major determinant of vascular tone in small resistance vessels. The influence of hyperhomocysteinemia on EDHF is unknown. The present in vivo study evaluates the integrity of the EDHF pathway in the renal microcirculation of rats with acute and chronic hyperhomocysteinemia. METHODS AND RESULTS: EDHF-mediated vasodilation was evaluated as the renal blood flow (RBF) response to intrarenal acetylcholine during systemic NO synthase and cyclooxygenase inhibition. Acute hyperhomocysteinemia induced by intravenous homocysteine did not affect EDHF-mediated vasodilation. In contrast, intravenous methionine with subsequent hyperhomocysteinemia impaired the EDHF-mediated RBF response. When the methionine infusion was preceded by adenosine periodate oxidized to prevent the cleavage of S-adenosylhomocysteine to homocysteine and adenosine, a similar impairment of EDHF was observed, but with normal homocysteine levels. Animals with chronic hyperhomocysteinemia induced by a high-methionine, low-B vitamin diet during 8 weeks had a severely depressed EDHF-mediated vasodilation compared with those on a standard diet. Endothelium-independent vasodilation to deta-NONOate and pinacidil was not affected in acute and chronic hyperhomocysteinemia, demonstrating intact vascular smooth muscle reactivity. CONCLUSIONS: EDHF-dependent responses are impaired in the kidney of hyperhomocysteinemic rats. Because EDHF is a major regulator of vascular function in small vessels, these findings have important implications for the development of microangiopathy in hyperhomocysteinemia.

Acetylcholine↗

PubMed2004

Long-term renal changes in the Goto-Kakizaki rat, a model of lean type 2 diabetes.

BACKGROUND: Type 2 diabetes has become the single most frequent cause of end-stage renal disease. The Goto-Kakizaki rat is currently used as a model for lean type 2 diabetes, but its renal changes have not been fully characterized. We investigated long-term functional and structural renal changes in the Goto-Kakizaki rat to evaluate if this animal model resembles the changes observed in human diabetic kidney disease. METHODS: Urinary albumin excretion, creatinine clearance and blood pressure were measured at the age of 2, 8 and 14 months in 12 female Goto-Kakizaki rats and 10 female, non-diabetic Wistar rats. To study kidney morphology, kidney weight, glomerular volume, basement membrane thickness, mesangial fraction and total mesangial volume were determined at 14 months. RESULTS: Urinary albumin excretion rose progressively over time in both groups, but was significantly higher in Goto-Kakizaki rats than in Wistar rats. Creatinine clearance decreased over time in Goto-Kakizaki rats but not in Wistar rats. Blood pressure was in the normotensive range in all animals throughout the study. Kidney weight, glomerular volume, basement membrane thickness, mesangial fraction and total mesangial volume were significantly higher in Goto-Kakizaki rats than in Wistar rats. Body weight and blood glucose levels were higher, whereas serum insulin levels were not different or lower in Goto-Kakizaki rats compared with Wistar rats. CONCLUSION: The Goto-Kakizaki rat is a lean, hyperglycaemic, euinsulinaemic, normotensive experimental model of type 2 diabetes with robust functional and structural renal changes.

Albuminuria↗

PubMed2004

Influence of adrenomedullin on tone of isolated bovine retinal arteries.

PURPOSE: To assess and characterize the vasorelaxing effect of adrenomedullin (AM) on isolated bovine retinal arteries (BRAs). METHODS: Retinal arteries were isolated from bovine eyes and mounted in a wire myograph for isometric tension recording. Concentration-response curves were generated by cumulative addition of AM (1 pM to 0.1 micro M) to the organ bath. RESULTS: AM caused a concentration-dependent relaxation of the BRAs. Removal of the endothelium of the BRAs, inhibition of nitric oxide synthase with -nitro-L-arginine (L-NA) or inhibition of soluble guanylyl cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly reduced the AM response. Cyclooxygenase inhibition with indomethacin or sodium diclofenac did not reduce, but rather increased, vasodilation. The AM-receptor antagonist AM 22-52 slightly, but significantly, reduced the AM response, whereas the CGRP-receptor antagonist CGRP 8-37 caused a more pronounced reduction. The adenosine receptor antagonist 8-(p-sulfophenyl) theophylline (8-SPT) did not affect AM-induced vasorelaxation. Inhibition of several intracellular calcium ([Ca(2+)](i))-reducing mechanisms failed to block the relaxation induced by AM. Only inhibition of the plasma membrane Ca(2+)-adenosine triphosphatase (ATPase) with vanadate significantly attenuated the AM response. CONCLUSIONS: AM induces vasodilation in isolated bovine retinal arteries. Endothelium-derived NO and stimulation of CGRP- and AM-receptors appear to be involved in the AM response, whereas prostanoids and activation of adenosine receptors are not involved. Activation of Ca(2+)-extrusion by the plasma membrane Ca(2+)-ATPase may elicit the relaxation of BRAs in response to AM.

Adrenomedullin↗

PubMed2002

Mesaconitine-induced relaxation in rat aorta: involvement of Ca2+ influx and nitric-oxide synthase in the endothelium.

Aconiti tuber, roots of aconite (Aconitum japonicum), is an oriental herbal medicine used for centuries in Japan and China to improve the health of persons with a weak constitution and poor metabolism. We investigated the effects of mesaconitine, one of the aconite alkaloids in Aconiti tuber, on the contraction and free intracellular Ca2+ concentration ([Ca2+]i) level in isolated rat thoracic aorta. Mesaconitine at 30 microM inhibited 3 microM phenylephrine-induced contraction in the endothelium-intact, but not endothelium-denuded, aortic rings. The effect of mesaconitine was dependent on external Ca2+ concentrations. The relaxation induced by mesaconitine was abolished by N(omega)-nitro-L-arginine methyl ester (0.1 mM, an inhibitor of nitric-oxide synthase), as well as the relaxation induced by acetylcholine. Acetylcholine induced relaxation in two phases in our conditions; the initial phase was transient and external Ca2+ -independent, and the second phase was sustained and external Ca2+ -dependent. Treatment with 100 nM thapsigargin, which depleted intracellular Ca2+ stores, inhibited acetylcholine-induced, but not mesaconitine-induced, relaxation. Mesaconitine increased the [Ca2+]i level in endothelial cells by influx of Ca2+ from extracellular spaces. These findings suggest that mesaconitine-induced Ca2+ influx and activation of nitric-oxide synthase in endothelial cells and, thus, induced vasorelaxation in rat aorta.

Aconitine↗

PubMed2002

Effects of connexin-mimetic peptides on nitric oxide synthase- and cyclooxygenase-independent renal vasodilation.

BACKGROUND: Research on the physiological role of endothelium-derived hyperpolarizing factor (EDHF) is hampered by the persistent controversy on its nature and mechanisms of action, as well as by the lack of specific inhibitors that are suitable for in vivo use. Recent in vitro studies support a role for gap junctions in EDHF-mediated signal transmission. The present study examines the contribution of gap junctional communication to the EDHF-mediated responses in the rat renal microcirculation in vivo and addresses the physiological role of EDHF. METHODS: The effects of intrarenal administration of connexin-mimetic peptides on the L-NAME- and indomethacin-resistant renal blood flow (RBF) response to acetylcholine, on basal RBF and on systemic blood pressure were examined. RESULTS: 43Gap 27, a peptide homologous to the second extracellular loop of connexin 43, partially inhibited the L-NAME- and indomethacin-resistant RBF response to acetylcholine, whereas 40Gap 27, homologous to the second extracellular loop of connexin 40, abolished the response. A control peptide, with a replacement of two amino acids in the motif SRPTEK present in the second extracellular loop of connexins 40 and 43, was without effect. None of the peptides affected the response to DETA-NONOate, pinacidil or papaverine. Intrarenal infusion of 43Gap 27 or 40Gap 27 decreased basal RBF and increased mean arterial blood pressure, both in the presence and absence of systemic infusion of L-NAME and indomethacin. CONCLUSIONS: Inhibition of gap junctional communication with connexin-mimetic peptides blocks EDHF-mediated signal transmission in vivo, as suggested by the abolishment of L-NAME- and indomethacin-resistant renal vasodilation. The peptides also decrease basal RBF and increase blood pressure, supporting a role for tonic EDHF release in the control of tissue perfusion and vascular resistance.

Acetylcholine↗

PubMed2002

Vasorelaxing effect of mesaconitine, an alkaloid from Aconitum japonicum, on rat small gastric artery: possible involvement of endothelium-derived hyperpolarizing factor.

Aconiti tuber, roots of aconite (Aconitum japonicum), has been used for centuries in Japan and China to increase peripheral body temperature. We previously reported that mesaconitine, an alkaloid from Aconitum japonicum, elicits endothelium-dependent and nitric oxide-mediated relaxation in isolated rat aorta. In the present study, we investigated the effect of mesaconitine on isolated rat small gastric arteries. Mesaconitine elicited a concentration-dependent (10, 30, 100 microM) vasorelaxation in isolated rat gastric artery precontracted with norepinephrine, which was resistant to N(omega)-nitro-L-arginine (L-NNA) (an inhibitor of nitric oxide synthase) and indomethacin (an inhibitor of cyclooxygenase). The L-NNA- and indomethacin-resistant relaxation by mesaconitine was mainly endothelium-dependent, inhibited by high K+ (30 mM), and inhibited by a combination of Ca2+-dependent K channel blockers, charybdotoxin and apamin. The relaxation by mesaconitine was proportional to the external Ca2+ concentration. These results suggest that mesaconitine elicits vasorelaxation of isolated rat small gastric artery mainly via release of endothelium-derived hyperpolarizing factor.

Aconitine↗

PubMed2002

Hemodynamic effects of peritoneal dialysis solutions on the rat peritoneal membrane: role of acidity, buffer choice, glucose concentration, and glucose degradation products.

Conventional peritoneal dialysis fluids (PDF) are unphysiologic because of their hypertonicity, high glucose and lactate concentrations, acidic pH, and presence of glucose degradation products (GDP). Long-term exposure to conventional PDF may cause functional and structural alterations of the peritoneal membrane. New PDF have a neutral pH, a low GDP content, and contain bicarbonate or lactate as the buffer. Intravital microscopy was used to analyze the vasoactive effects of conventional and new PDF on the rat peritoneal membrane. A conventional, acidic pH, lactate-buffered 4.25% glucose PDF induced maximal vasodilation of mesenteric arteries, resulting in a doubling of the arteriolar flow and a 20% increase of the perfused capillary length per area. The hemodynamic effects of conventional PDF were similar after pH-adjustment with NaOH, indicating that acidity per se is not essential for the changes. Superfusion by a pH-neutral, lactate-buffered PDF with low GDP content caused only a transient arterial vasodilation despite continuous exposure, with a commensurate effect on arteriolar flow and capillary recruitment. Application of a pH-neutral, bicarbonate-buffered PDF with low GDP content did not affect the hemodynamic parameters. Resterilization of the bicarbonate solution increased GDP levels and completely restored the vasodilatory capacity. The corresponding 1.5% glucose PDF induced similar but less pronounced changes. Conventional PDF have important vasoactive effects on the peritoneal circulation, mainly because of the presence of GDP and transiently because of high lactate concentrations. Capillary recruitment may increase effective peritoneal vascular surface area. In addition, chronic vasodilation may induce structural adaptations in the blood vessel wall, contributing to vascular sclerosis. PDF with reduced GDP content induce no major hemodynamic effects and may thus have the potential to better preserve peritoneal vascular integrity.

Acids↗

PubMed2002

Rat retinal tissue releases a vasorelaxing factor.

PURPOSE: To investigate whether the retina of the rat exerts a vasodilatory influence by the release of a relaxing factor and to characterize the retinal relaxing factor (RRF). METHODS: The relaxing influence of the rat retina was investigated by placing the retina in close proximity with a precontracted isolated rat carotid artery ring segment, mounted for isometric tension measurements. RESULTS: Application of rat retina relaxed the artery in a reliable and reproducible way. The nitric oxide (NO)-synthase inhibitor N(omega)-nitro-L-arginine (L-NA), the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and the removal of the endothelium of the artery all failed to affect the RRF response. The RRF response was not decreased; in contrast, it increased after treatment with a cyclooxygenase (COX) inhibitor (indomethacin or sodium diclofenac). Acute hypoxia largely enhanced retina-induced relaxation. Several potential mediators of hypoxia-induced vasodilation were excluded as candidates for the RRF or for mediating the enhanced response to RRF in hypoxia. Inhibition of the plasma membrane Ca(2+)-adenosine triphosphatase (ATPase) with vanadate significantly affected the RRF response. CONCLUSIONS: The release of an as yet unidentified relaxing factor(s) from the rat retina was demonstrated. Acute hypoxia profoundly enhances the RRF response. None of the known mediators of hypoxia-induced vasodilation nor NO, prostanoids, or endothelial factors mediate the RRF response. Activation of the plasma membrane Ca(2+)-ATPase seems to be involved in the RRF response.

Acute Disease↗

PubMedDate not supplied

A vasorelaxing factor is released from mouse retinal tissue.

The present study aimed to demonstrate the release of a retinal relaxing factor (RRF) from the retina of mice and to investigate the identity of the RRF. Ring segments of a mouse aorta were mounted in a small vessel myograph. The relaxing influence of mouse retinal tissue was assessed by placing a retina in close proximity to the precontracted aorta. This elicited reliable and reproducible relaxations in the aorta. Both the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine and the soluble guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one had no effect on the RRF response. Also the cyclooxygenase inhibitors indomethacin and sodium diclofenac failed to affect the retina-induced relaxations. Acute hypoxia largely enhanced retina-induced relaxations. It is concluded that mouse retinal tissue releases an RRF, that the mouse RRF response is not mediated by NO or prostanoids and that the mouse RRF response is profoundly influenced by hypoxia.

Acute Disease↗