Acute superoxide scavenging restores depressed baroreflex sensitivity in renovascular hypertensive rats

Abstract

In some pathological conditions such as hypertension, there is an impairment in the autonomic control of blood pressure resulting in changes in baroreflex sensitivity. In the present study we tested the hypothesis that acute superoxide scavenging would restore the reduced baroreflex sensitivity in renovascular hypertension. Male Wistar rats underwent 2-Kidney-1-Clip (2K1C) or sham surgery and were maintained untouched for six weeks to develop hypertension. After six weeks, animals from the 2K1C group were hypertensive when compared to the sham group (165 ± 9 vs. 108 ± 7 mmHg, P < 0.05). As a proof of principle for the hypertension model adopted, animals from the 2K1C group presented increased non-clipped kidney and cardiac mass index and reduced clipped kidney mass index. Regarding baroreflex, 2K1C rats presented diminished baroreflex sensitivity when compared to the sham group (2K1C + saline: −1.61 ± 0.15 vs. sham + saline: −2.79 ± 0.24 bpm mm Hg −1, p < 0.05). Moreover, acute administration of Vitamin C (150 mg/Kg, i.v.) restored baroreflex sensitivity in 2K1C rats (2K1C + Vit C: −3.08 ± 0.37 vs. 2K1C + saline: −1.61 ± 0.15 bpm mm Hg −1, p < 0.05). Furthermore, administration of apocynin (30 μg/Kg, i.v.), a NADPH oxidase inhibitor, also improved baroreflex sensitivity in the 2K1C group (2K1C + apocynin: −2.81 ± 0.24 vs. 2K1C + saline: −1.61 ± 0.15 bpm mm Hg −1, p < 0.05). In addition, autonomic blockade with either methylatropine or propranolol reduced the changes in heart rate to the same extent in all groups suggesting that improved baroreflex sensitivity by antioxidants were mediated by improvement in autonomic function. Taken together, these data suggest that NADPH oxidase-derived reactive oxygen species are involved in the blunted baroreflex sensitivity in renovascular hypertension and that acute scavenging of superoxide restores baroreflex sensitivity.