Beneficial Effects of Renal Denervation on Pulmonary Vascular Remodeling in Experimental Pulmonary Artery Hypertension

Activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system is closely associated with pulmonary arterial hypertension. We hypothesized that renal denervation decreases renin-angiotensin-aldosterone activity and inhibits the progression of pulmonary arterial hypertension. Twenty-two beagles were randomized into 3 groups. The dogs’ pulmonary dynamics were measured before and 8 weeks after injection of 0.1mL/kg dimethylformamide (control dogs) or 2mg/kg dehydromonocrotaline (pulmonary arterial hypertension and pulmonary arterial hypertension + renal denervation dogs). Eight weeks after injection, neurohormone levels and pulmonary tissue morphology were measured. Levels of plasma angiotensin II and endothelin-1 were significantly increased after 8 weeks in the pulmonary arterial hypertension dogs and were higher in the lung tissues of these dogs than in those of the control and renal denervation dogs (mean [standard deviation] angiotensin II: 65 [9.8] vs 38 [6.7], 46 [8.1]; endothelin-1: 96 [10.3] vs 54 [6.2], 67 [9.4]; P < .01). Dehydromonocrotaline increased the mean pulmonary arterial pressure (16 [3.4] mmHg vs 33 [7.3] mmHg; P < .01), and renal denervation prevented this increase. Pulmonary smooth muscle cell proliferation was higher in the pulmonary arterial hypertension dogs than in the control and pulmonary arterial hypertension + renal denervation dogs. Renal denervation attenuates pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental pulmonary arterial hypertension. The effect of renal denervation may contribute to decreased neurohormone levels. La activación tanto del sistema nervioso simpático como del sistema renina-angiotensina-aldosterona está estrechamente relacionada con la hipertensión arterial pulmonar. Nuestra hipótesis era que la simpatectomía renal reduce la actividad del sistema renina-angiotensina-aldosterona e inhibe la progresión de la hipertensión arterial pulmonar. Se asignó aleatoriamente a un total de 22 perros beagle a tres grupos de estudio. Se efectuaron determinaciones de la dinámica pulmonar de esos animales antes y 8 semanas después de la inyección de 0,1 ml/kg de dimetilformamida (perros de control) o de 2 mg/kg de deshidromonocrotalina (perros con hipertensión arterial pulmonar y perros con hipertensión arterial pulmonar + simpatectomía renal). Ocho semanas después de la inyección, se determinaron las concentraciones de neurohormonas y se evaluó la morfol