Efectos beneficiosos de la simpatectomía renal sobre el remodelado vascular pulmonar en la hipertensión arterial primaria experimental / Beneficial effects of renal denervation on pulmonary vascular remodeling in experimental pulmonary artery hypertension

Introducción y objetivos. 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. Métodos. 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 morfología del tejido pulmonar. Resultados. Se observó un aumento significativo de la concentración de angiotensina II y endotelina-1 en plasma después de 8 semanas en los perros con hipertensión arterial pulmonar, y los valores obtenidos en los tejidos pulmonares de estos animales eran superiores a los de los perros del grupo de control y el grupo de simpatectomía renal (medias: angiotensina II, 65 ± 9,8 frente a 38 ± 6,7 y 46 ± 8,1; endotelina-1, 96 ± 10,3 frente a 54 ± 6,2 y 67 ± 9,4; p < 0,01). La deshidromonocrotalina aumentó la presión arterial pulmonar media (16 ± 3,4 frente a 33 ± 7,3 mmHg; p < 0,01), y la simpatectomía renal evitó que se produjera este aumento. La proliferación celular del músculo liso pulmonar fue mayor en los perros con hipertensión arterial pulmonar que en los animales de los grupos de control y de hipertensión arterial pulmonar + simpatectomía renal. Conclusiones. La simpatectomía renal atenúa el remodelado vascular pulmonar y reduce la presión arterial pulmonar en la hipertensión arterial pulmonar experimental. El efecto de la simpatectomía renal puede contribuir a reducir las concentraciones de neurohormonas (AU)

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 0.1 mL/kg dimethylformamide (control dogs) or 2 mg/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 (AU)

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

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.