Treatment with Nesiritide, A Recombinant B-Type Natriuretic Peptide, Reduces Vascular Remodeling Following Balloon-Induced Endothelial Injuries in Rabbits

Abstract

Re-stenosis or remodeling of coronary and peripheral arteries remains a major complication following balloon-angioplasty or stenting. This study was designed to investigate the effect of nesiritide, a recombinant B-type natriuretic peptide (BNP), on vascular remodeling following balloon-induced endothelial injuries. Twenty-eight male New Zealand rabbits were divided into nesiritide-treated (0.1 mg/kg/day, sc, for 4 weeks, n = 10), saline-treated control (n = 10) and sham-operated groups (n = 8). In the nesiritide and control groups, a balloon catheter was inserted to the right iliac artery to induce injuries. Vascular endothelial growth factor (VEGF) was measured by immunohistochemistry. The area under internal elastic membrane of the arterial wall (643.2 ± 134.1 vs 493.7 ± 139.3 μ m², p < 0.05) and the area under external elastic membrane (1495.1 ± 204.9 vs 1265.9 ± 232.6 μ m², p < 0.05) in the nesiritide group were greater than those in the control group, but were smaller than those in the sham-operated group (p < 0.05). The stenosis ratio was lower in the nesiritide group than in the control group (18.7 ± 7.7% vs 38.0 ± 8.3%, p < 0.01). Importantly, the VEGF expression rate was significantly lower in the nesiritide group than in the control group (42.2 ± 8.8% vs 56.1 ± 13.1%, p < 0.05), while there were no signs of VEGF expression in the non-injured arteries of the three groups. In conclusion, nesiritide treatment reduces the stenosis of the rabbit iliac artery following balloon-induced endothelial injuries probably by decreasing VEGF expression.

Recombinant B-type Natriuretic Peptide Nesiritide Attenuates Vascular Remodelling by Reducing Plasma Aldosterone in Rabbits

“…Twenty-four healthy New Zealand male rabbits (weight 2.5-2.8 kg, age 4-6 months) were divided into nesiritide (n = 12) and control (n = 12) group. After general anaesthesia (ketamine, 20 mg/kg, iv), an ultrasound-guided balloon catheter (2.0 mm × 20 mm, Medtronic, MN, USA) was inserted through the right femoral artery to the common iliac artery [9]. The balloon was inflated with saline until the pressure reached 5 atm.…”

“…It was then advanced to the common iliac artery and inflated with 5 atm pressure, and pulled back to the right femoral artery again. This procedure was repeated four times to create endothelial injuries to the iliac and the right femoral artery [9]. The balloon catheter was then withdrawn and the arterial incision was closed with small nylon sutures.…”

“…The nesiritide group animals were subcutaneously injected with nesiritide (0.1 mg/kg/day diluted with normal saline, Shanghai GL Biochem, Shanghai, China) once daily for 28 days. This dose was chosen as in our previous studies in the same animal model it had significant impact on vascular remodelling [9]. The same volume of normal saline as in the nesiritide group was subcutaneously injected to the control group animals daily for 28 days.…”

“…Furthermore, circulating aldosterone but levels were independently related to echocardiographic parameters of left ventricular structure, and higher serum aldosterone level was related to concentric left ventricular hypertrophy [14]. whether aldosterone plays any role in the prevention of cardiovascular remodelling following nesiritide treatment [4,7,9]. In this study, we investigated the relations between plasma aldosterone levels and vascular remodelling following nesiritide therapy in a rabbit model.…”

“…In mice, nesiritide decreases hypertrophy of heart muscles by elevating cGMP concentrations [8]. Our recent study in rabbits showed that nesiritide treatment reduced the stenosis of the iliac artery following balloon-induced endothelial injuries [9]. The mechanisms of nesiritide on cardiovascular remodelling are unclear.…”