Parasympathetic activity is often reduced in hypertension and can elicit anti-inflammatory mechanisms. Thus, we hypothesized that chronic vagal nerve stimulation (VNS) may alleviate cardiovascular end-organ damage in stroke-prone spontaneously hypertensive rats. Vagal nerve stimulators were implanted, a high-salt diet initiated, and the stimulators turned on (VNS, n=10) or left off (Sham, n=14) for 4 weeks. Arterial pressure increased equally in both groups. After 4 weeks, endothelial function, assessed by in vivo imaging of the long posterior ciliary artery (LPCA) after stimulation (pilocarpine) and inhibition (L-NAME) of endothelial nitric oxide synthase (eNOS), had significantly declined (-2.3±1.2 µm, P<0.05) in Sham but was maintained (-0.7±0.8 µm, NS) in VNS. Furthermore, aortic eNOS activation (phosphorylated to total eNOS protein content ratio) was greater in VNS (0.83±0.07) than in Sham (0.47±0.08, P<0.05). After only 3 weeks, ultrasound imaging of the aorta demonstrated decreased aortic strain (-9.7±2.2%, P<0.05) and distensibility (-2.39±0.49 1000/mmHg, P<0.05) and increased pulse wave velocity (+2.4±0.7 m/s, P<0.05) in Sham but not in VNS (-3.8±3.8%, -0.70±1.4 1000/mmHg, and +0.1±0.7 m/s, all NS). Interleukin 6 (IL-6) serum concentrations tended to be higher in VNS than in Sham (34.3±8.3 pg/mL vs. 16.1±4.6 pgm/mL, P=0.06) and positive correlations were found between NO-dependent relaxation of the LPCA and serum levels of IL-6 (r=+0.70, P<0.05) and IL-10 (r=+0.56, P<0.05) and between aortic eNOS activation and IL-10 (r=+0.48, P<0.05). In conclusion, chronic VNS prevents hypertension-induced endothelial dysfunction and aortic stiffening in an animal model of severe hypertension. We speculate that anti-inflammatory mechanisms may contribute to these effects.
- cardiovascular end-organ damage
- nitric oxide-dependent relaxation
- aortic distensibility
- parasympathetic nervous system
- Copyright © 2016, American Journal of Physiology - Heart and Circulatory Physiology