Hematologic responses and the early development of hypoxic pulmonary hypertension in rats

Hill, Nicholas S.; Petit, R; Gagnon, Jeanne; Warburton, Rod R.; Ou, L.C.

doi:10.1016/0034-5687(93)90104-i

Cited by 7 publications

(4 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A study using rats exposed to a hypobaric hypoxia protocol (21 days at 0.5 atm; PB 380 mm Hg) showed an increase in the relative number of reticulocytes on day 3, reaching the maximum on day 7, before returning to normal levels on day 14. However, the reticulocytes reached a new peak on day 21 of the protocol [52]. These results suggest a negative feedback on the hypoxia-induced reticulocytes formation, which reaches its maximum after 5–7 days of hypoxia before decreasing to normal levels, as we have described here.…”

Section: Discussionsupporting

confidence: 75%

Expression Profiling Reveals Novel Hypoxic Biomarkers in Peripheral Blood of Adult Mice Exposed to Chronic Hypoxia

et al. 2012

View full text Add to dashboard Cite

Hypoxia induces a myriad of changes including an increase in hematocrit due to erythropoietin (EPO) mediated erythropoiesis. While hypoxia is of importance physiologically and clinically, lacunae exist in our knowledge of the systemic and temporal changes in gene expression occurring in blood during the exposure and recovery from hypoxia. To identify these changes expression profiling was conducted on blood obtained from cohorts of C57Bl-10 wild type mice that were maintained at normoxia (NX), exposed for two weeks to normobaric chronic hypoxia (CH) or two weeks of CH followed by two weeks of normoxic recovery (REC). Using stringent bioinformatic cut-offs (0% FDR, 2 fold change cut-off), 230 genes were identified and separated into four distinct temporal categories. Class I) contained 1 transcript up-regulated in both CH and REC; Class II) contained 202 transcripts up-regulated in CH but down-regulated after REC; Class III) contained 9 transcripts down-regulated both in CH and REC; Class IV) contained 18 transcripts down-regulated after CH exposure but up-regulated after REC. Profiling was independently validated and extended by analyzing expression levels of selected genes as novel biomarkers from our profile (e.g. spectrin alpha-1, ubiquitin domain family-1 and pyrroline-5-carboxylate reductase-1) by performing qPCR at 7 different time points during CH and REC. Our identification and characterization of these genes define transcriptome level changes occurring during chronic hypoxia and normoxic recovery as well as novel blood biomarkers that may be useful in monitoring a variety of physiological and pathological conditions associated with hypoxia.

show abstract

Section: Discussionsupporting

confidence: 75%

Expression Profiling Reveals Novel Hypoxic Biomarkers in Peripheral Blood of Adult Mice Exposed to Chronic Hypoxia

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Arrows indicate barium-filled arteries. hypoxia in the altitude-susceptible H strain of SDR in comparison with the resistant M strain, although hematocrit did not differ between the strains until 21 days of hypoxia (18). We speculate that brief perinatal hypoxia caused subtle alterations in the erythropoietic system, which did not lead to striking elevation in hematocrit until triggered by hypoxia later in infancy.…”

Section: Discussionmentioning

confidence: 75%

Brief perinatal hypoxia increases severity of pulmonary hypertension after reexposure to hypoxia in infant rats

Tang

Cras

2000

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

We hypothesized that disrupted alveolarization and lung vascular growth caused by brief perinatal hypoxia would predispose infant rats to higher risk for developing pulmonary hypertension when reexposed to hypoxia. Pregnant rats were exposed to 11% inspired oxygen fraction (barometric pressure, 410 mmHg; inspired oxygen pressure, 76 mmHg) for 3 days before birth and were maintained in hypoxia for 3 days after birth. Control rats were born and raised in room air. At 2 wk of age, rats from both groups were exposed to hypoxia for 1 wk or kept in room air. We found that brief perinatal hypoxia resulted in a greater increase in right ventricular systolic pressure and higher ratio of right ventricle to left ventricle plus septum weights after reexposure to hypoxia after 2 wk of age. Moreover, perinatal hypoxic rats had decreased radial alveolar counts and reduced pulmonary artery density. We conclude that brief perinatal hypoxia increases the severity of pulmonary hypertension when rats are reexposed to hypoxia. We speculate that disrupted alveolarization and lung vascular growth following brief perinatal hypoxia may increase the risk for severe pulmonary hypertension with exposure to adverse stimuli later in life.

show abstract

“…Hypoxic exposure stabilizes HIF-1 in vitro, and thus the rapid increase in vascular expression of HO-1 could be regulated directly by hypoxia (26). Alternatively, CH induces polycythemia, which increases blood viscosity and thus shear stress on the vascular wall (14). Shear stress has been shown to enhance HO-1 gene expression in cultured VSMC (39).…”

mentioning

confidence: 99%

“…In addition, it has also been suggested that HO enzyme activity could be stimulated by additional heme availability due to increased free hemoglobin during polycythemia (31). Because polycythemia is a slowly developing characteristic of hypoxic exposure (14,34), observation of an early onset of hyporeactivity and HO expression would support hypoxia per se as a likely stimulus for these responses. Similarly, polycythemia is sustained upon restoration of normoxia after CH.…”

mentioning

confidence: 99%

Correlation of HO-1 expression with onset and reversal of hypoxia-induced vasoconstrictor hyporeactivity

Jernigan

O'Donaughy

Walker

2001

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Rats exposed to chronic hypoxia (CH; 4 wk at 0.5 atm) exhibit attenuated renal vasoconstrictor reactivity to phenylephrine (PE). Preliminary studies from our laboratory suggest that this response is mediated by hypoxic induction of heme oxygenase (HO) and subsequent release of the endogenous vasodilator carbon monoxide. Because vascular HO mRNA is increased within hours of hypoxic exposure, we hypothesized that the onset of reduced reactivity may occur fairly rapidly and correlate with HO expression. Therefore, we examined the onset of attenuated vasoconstriction on CH exposure as well as the duration of hyporeactivity on return to a normoxic environment. Renal vascular resistance (RVR) responses to graded intravenous infusion of PE were measured in conscious rats under control conditions and after 24 h, 48 h, and 4 wk of CH exposure. Vasoreactivity responses were also determined in 4-wk CH rats 1, 5, 24, and 96 h after return to normoxia. We found that RVR responses to PE were significantly blunted after 48 h and 4 wk but not after 24 h of hypoxic exposure. Inhibition of HO with zinc protoporphyrin IX increased RVR and decreased renal blood flow in 48-h CH rats but not controls. Although reactivity to PE was gradually restored after 4 wk of CH, responsiveness was still slightly blunted at 96 h after return to normoxia. Western blot analysis demonstrated a correlation between HO-1 protein levels and attenuated vasoconstrictor response in CH and posthypoxic rats. These data suggest that the onset and offset of physiologically relevant vascular HO expression occur within 2--3 days.

show abstract

Hematologic responses and the early development of hypoxic pulmonary hypertension in rats

Cited by 7 publications

References 16 publications

Expression Profiling Reveals Novel Hypoxic Biomarkers in Peripheral Blood of Adult Mice Exposed to Chronic Hypoxia

Expression Profiling Reveals Novel Hypoxic Biomarkers in Peripheral Blood of Adult Mice Exposed to Chronic Hypoxia

Brief perinatal hypoxia increases severity of pulmonary hypertension after reexposure to hypoxia in infant rats

Correlation of HO-1 expression with onset and reversal of hypoxia-induced vasoconstrictor hyporeactivity

Contact Info

Product

Resources

About