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

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±11.7mm Hg) compared with sham group (192.4±10.5/141.2±5.9mm 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.

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