Constant daily hypoxia leads to different degrees of pulmonary hypertension in two different rat strains

Chadi E Bouserhal,Erik Van Lunteren,Frank J Jacono,Kingman P Strohl

doi:10.4236/ojmip.2012.23012

Chadi E Bouserhal, Erik Van Lunteren + Show 2 more

Open Access

https://doi.org/10.4236/ojmip.2012.23012

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Abstract

Pulmonary diseases associated with diurnal hypoxemia are known to be associated with pulmonary hypertension in some patients. In this study we examined the effects of daily hypoxia (10% oxygen; 8h/day for 14 days) on two strains of rats to simulate sleep related hypoxia in pulmonary diseases expecting to find differences in vascular responses, the develop-ment of right ventricular hypertrophy and pulmonary hypertension according to genetic background. In response to daily hypoxia, Sprague Dawley rats developed right ventricular hypertrophy while Brown Norway rats did not. Both strains developed pulmonary hypertension (elevated right ventricular pressure) although the increase was significantly greater in the Sprague Dawley strain. Pulmonary artery (first branch) vasoconstrictive responses to potassium chloride were increased equally in both strains and the subsequent vasodilation with acetylcholine were reduced equally with daily hypoxia in both strains. Taken together, these findings suggest that the genetic makeup of the rats contributed significantly to the development of right ventricular hypertrophy and the degree of pulmonary hypertension. Moreover, this response is not secondary to differences in the intralobar pulmonary vascular reactivity. Genetic background could explain why certain patients do worse with hypoxia inducing pulmonary vascular diseases.

Highlights

The incidence of pulmonary hypertension in chronic obstructive and interstitial lung diseases is dependent on the disease, the degree of hypoxia and possibly an individual’s genetic response [1,2,3,4]
In-vivo measurements of right ventricular pressure (RVP) showed a significant increase in pressure when Sprague Dawleys were conditioned with 2 weeks of eight hour constant daily hypoxia compared to normoxic controls; this increase of pressure was present in the Brown Norway strain after hypoxic exposure (Figure 1)
Right ventricular hypertrophy occurred in Sprague Dawley rat strain as manifested by the significant increase of RV left ventricle (LV) Septum ratio in hypoxia conditioned rats (Figures 3 and 4)

Summary

Introduction

The incidence of pulmonary hypertension in chronic obstructive and interstitial lung diseases is dependent on the disease, the degree of hypoxia and possibly an individual’s genetic response [1,2,3,4]. The development of pulmonary hypertension has been examined in rat strains exposed to continuous steady-state hypoxia. In these animal models, measured physiologic differences included vascular reactivity and right ventricular hypertrophy [7]. Thomas et al showed that the physiologic response to continuous hypoxia was a graded response that starts with an increase in pulmonary vascular reactivity followed by an increase in right ventricular pressure and right ventricular hypertrophy [8]. Jin et al reported that the Sprague Dawley rat strain developed significantly less vascular reactivity than that developed by the Wistar rat strain, indicating a role for genetic predisposition in the response to hypoxia [7]

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