Response of the Renal Inner Medulla to Hypoxia: Possible Defense Mechanisms

Kim, Namhee; Voicu, Laura; Hare, Gregory M. T.; Cheema‐Dhadli, Surinder; Chong, Chee Kiong; Chan, Stephen K W; Bichet, Daniel G.; Halperin, Mitchell L.; Mazer, C. David

doi:10.1159/000345516

Cited by 5 publications

(7 citation statements)

References 33 publications

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“…This confirms that telemetry implantation does not affect the development of experimental pulmonary hypertension [4,12]. The haematocrit in SuHx rats increased significantly during the hypoxic period, which has been reported to be related to a combined effect of diuresis and intensified erythropoiesis [20]. The correlation between haematocrit and RVSP during the exposure to hypoxia suggests that some of the pressure increase in SuHx rats is related to an increase in blood viscosity.…”

Section: Serial Haemodynamic and Histological Characterisationsupporting

confidence: 77%

SuHx rat model: partly reversible pulmonary hypertension and progressive intima obstruction

et al. 2014

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The SU5416 combined with hypoxia (SuHx) rat model features angio-obliterative pulmonary hypertension resembling human pulmonary arterial hypertension. Despite increasing use of this model, a comprehensive haemodynamic characterisation in conscious rats has not been reported.We used telemetry to characterise haemodynamic responses in SuHx rats and associated these with serial histology.Right ventricular systolic pressure (RVSP) increased to a mean¡SD of 106¡7 mmHg in response to SuHx and decreased but remained elevated at 72¡8 mmHg upon return to normoxia. Hypoxia-only exposed rats showed a similar initial increase in RVSP, a lower maximum RVSP and near-normalisation of RVSP during subsequent normoxia. Progressive vascular remodelling consisted of a four-fold increase in intima thickness, while only minimal changes in media thickness were found. The circadian range in RVSP provided an accurate longitudinal estimate of vascular remodelling.In conclusion, in SuHx rats, re-exposure to normoxia leads to a partial decrease in pulmonary artery pressure, with persisting hypertension and pulmonary vascular remodelling characterised by progressive intima obstruction. @ERSpublications Telemetry studies can facilitate preclinical studies to further improve our understanding of drug actions in PAH

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Section: Serial Haemodynamic and Histological Characterisationsupporting

confidence: 77%

SuHx rat model: partly reversible pulmonary hypertension and progressive intima obstruction

et al. 2014

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“…The body mass at week 6 is equally lowered in SuHx and SuPNx rats, although SuHx rats show a temporally more profound decline in body mass compared with SuPNx rats in week 2. This phenomenon is probably explained by a combi- nation of hypoxia-induced diuresis and anorexia that lowers body mass (16).…”

Section: Discussionmentioning

confidence: 99%

Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats

Happé

Raaf

Rol

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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The SU5416 + hypoxia (SuHx) rat model is a commonly used model of severe pulmonary arterial hypertension. While it is known that exposure to hypoxia can be replaced by another type of hit (e.g., ovalbumin sensitization) it is unknown whether abnormal pulmonary blood flow (PBF), which has long been known to invoke pathological changes in the pulmonary vasculature, can replace the hypoxic exposure. Here we studied if a combination of SU5416 administration combined with pneumonectomy (PNx), to induce abnormal PBF in the contralateral lung, is sufficient to induce severe pulmonary arterial hypertension (PAH) in rats. Sprague Dawley rats were subjected to SuPNx protocol (SU5416 + combined with left pneumonectomy) or standard SuHx protocol, and comparisons between models were made at week 2 and 6 postinitiation. Both SuHx and SuPNx models displayed extensive obliterative vascular remodeling leading to an increased right ventricular systolic pressure at week 6 Similar inflammatory response in the lung vasculature of both models was observed alongside increased endothelial cell proliferation and apoptosis. This study describes the SuPNx model, which features severe PAH at 6 wk and could serve as an alternative to the SuHx model. Our study, together with previous studies on experimental models of pulmonary hypertension, shows that the typical histopathological findings of PAH, including obliterative lesions, inflammation, increased cell turnover, and ongoing apoptosis, represent a final common pathway of a disease that can evolve as a consequence of a variety of insults to the lung vasculature.

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“…In fact, there is evidence that urine concentrating ability by the renal medulla in the rat is the earliest indicator of renal hypoxia. 27…”

Section: Discussionmentioning

confidence: 99%

Anemia increases the risk of renal cortical and medullary hypoxia during cardiopulmonary bypass

et al. 2013

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The clear difference in the degree of hypoxia in the renal cortex and medulla may be useful in understanding the progress of medullary hypoxia during CPB with anemia and the potential development of AKI. Further studies should aim at identifying early markers of medullary hypoxia and potential agents that may decrease the work and O2 consumption in the renal medulla to reduce the risk of hypoxic damage during CPB and anemia.

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Response of the Renal Inner Medulla to Hypoxia: Possible Defense Mechanisms

Cited by 5 publications

References 33 publications

SuHx rat model: partly reversible pulmonary hypertension and progressive intima obstruction

SuHx rat model: partly reversible pulmonary hypertension and progressive intima obstruction

Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats

Anemia increases the risk of renal cortical and medullary hypoxia during cardiopulmonary bypass

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