A Novel Swine Model of Spontaneous Hypertension With Sympathetic Hyperactivity Responds Well to Renal Denervation.

ABSTRACT

BACKGROUND: The large animal model of arterial hypertension is very valuable to test the antihypertensive drugs and devices. We characterized a novel swine model of spontaneous hypertension and investigated its response to renal denervation (RDN). METHODS: The blood pressure (BP), levels of plasma catecholamines and urine vanillylmandelic acid, and the protein expressions of angiotensin-converting enzyme (ACE) and angiotensin II type 1 (AT1), and type 2 (AT2) receptors in the rostral ventrolateral medulla (RVLM) were compared between domestic pigs and Guizhou mini-pigs. Twelve-month-old Guizhou mini-pigs were divided into sham (n = 7) and ablation (n = 7) groups. The mini-pigs in ablation group received bilateral percutaneous RDN with a saline-irrigated Sniper ablation catheter. Three months after the procedure, the BP was measured and the histology of renal nerves and arteries was analyzed. RESULTS: The mini-pigs spontaneously developed hypertension by the age of 6 months and the BP (162.2 ± 11.4/111.8 ± 9.2mm Hg) was significantly higher than age-matched domestic pigs (137.5 ± 1.9/80.2 ± 4.1mm Hg, P < 0.05). The levels of plasma catecholamines and urine vanillylmandelic acid were higher in mini-pigs than domestic pigs. The expressions of ACE and AT1 were increased, but the AT2 was decreased, in RVLM from mini-pigs compared with domestic pigs. Three months after the procedure, the BP was sharply reduced in ablation group (113.8 ± 14.4/79.4 ± 11.7 mm Hg) compared with sham group (192.4 ± 10.5/141.2 ± 5.9 mm Hg, P < 0.01). Renal nerves were substantially destroyed, while renal arteries and function were not significantly affected by ablation. CONCLUSIONS: The Guizhou mini-pig is a novel spontaneous hypertensive animal model with sympathetic hyperactivity and responds well to RDN.