Characterisation of a rat model of pulmonary arterial hypertension.

INTRODUCTION

Pulmonary hypertension portends an adverse outcome. Animal models have improved current understanding of the complex pathophysiology of the disease, but may be technically demanding. Moreover, plexiform vascular lesions are rarely observed, limiting the extrapolation to human pathophysiology. The aim of the present study was first, to assess the feasibility of closed-chest pressure recordings, and mainly, to further characterise a new model of endothelin receptor-B deficient rats.

METHODS

Jugular venous catheterisation was assessed in 15 Wistar rats. Pressure recordings via a left lateral thoracotomy and histological findings were compared in three rat groups (age 20 +/- 1 weeks, weight 200-250 g): (a) wild type (n = 10, group A); (b) wild type after monocrotaline injection (n=10, group B); and (c) endothelin receptor-B deficient rats (n = 10, group C) after monocrotaline injection.

RESULTS

Pressure recordings via the jugular approach were feasible in only 3 (20%) rats. Compared to group A, there was a trend (H = 4.6, p = 0.0962) towards increased mortality in groups B and C, due to respiratory arrest during intubation attempts. Pulmonary artery systolic pressure in group C was 24.7 +/- 1.3 mmHg, higher than in group B (21.5 +/- 1.2, p = 0.036) or group A (11.8 +/- 0.5, p < 0.0001). Adverse pulmonary vascular remodelling was more prominent in group C than in group B.

CONCLUSIONS

Endothelin receptor-B deficient rats constitute a useful model of pulmonary artery hypertension after monocrotaline injection. The ease of pressure recordings via a left lateral thoracotomy may aid in the more widespread use of this model.