Depressed Baroreflex Sensitivity in Hypertensive Rats: A Role for Reactive Oxygen Species

Abstract

One of the key mechanisms in controlling blood pressure in health and disease is the baroreflex. Baroreceptors located in the carotid sinuses and aortic arch detect changes in blood pressure and trigger reflex autonomic adjustments that buffer alterations in blood pressure. In pathological conditions such as hypertension, there is impairment in the autonomic control of blood pressure resulting in changes in baroreflex sensitivity [4-6]. Indeed, compelling evidence show that the baroreflex modulation of heart rate is impaired in spontaneously hypertensive rats and patients with primary hypertension [6,7]. We have recently demonstrated that acute antioxidant therapy improves baroreflex sensitivity in models of primary (essential) and secondary hypertension [5,6]. In a model of renovascular hypertension, the 2-kidney-1-clip (2K1C), we have shown that acute treatment with Vitamin C (150 mg/Kg, i.v.), a well-known antioxidant, restored the depressed baroreflex sensitivity in those hypertensive animals [5]. Furthermore, administration of apocynin (30 µg/Kg, i.v.), a NADPH oxidase inhibitor, improved baroreflex sensitivity in the 2K1C group. In the same study, autonomic blockade with either methylatropine or propranolol reduced the changes in heart rate to the same extent in normotensive and hypertensive groups suggesting that improved baroreflex sensitivity by antioxidants were mediated by improvement in autonomic function. Taken together, those data suggest that NADPH oxidase-derived reactive oxygen species are involved in the blunted baroreflex sensitivity in secondary hypertension and that acute scavenging of superoxide restores baroreflex sensitivity. Regarding primary hypertension, we have also demonstrated in spontaneously