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

Abstract

Introduction and objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Ablación; Ablation; Angiotensin II; Angiotensina II; Endotelina; Endothelin; Hipertensión arterial pulmonar; Inervación simpática renal; Pulmonary arterial hypertension; Renal sympathetic nerve.