Inhibition of sympathetic activity by rilmenidine reverses angiotensin II-induced hypertension, blood pressure variability and cardiac remodeling

S SELECTED FOR PRESENTATION 14.4 Inhibition of sympathetic activity by rilmenidine reverses angiotensin II-induced hypertension, blood pressure variability and cardiac remodeling R. Sabharwal, R.N. El Accaoui, R.M. Weiss, M.K. Davis, F.M. Abboud, M.W. Chapleau Department of Internal Medicine, University of Iowa Veterans Affairs Medical Center, USA The relative contribution of increased sympathetic activity to angiotensin II (Ang II)-induced hypertension and end-organ damage is controversial. To determine the importance of the sympathetic nervous system, we examined whether sustained inhibition of sympathetic activity induced by intracerebroventricular infusion of rilmenidine (RIL) attenuates Ang II-induced hypertension, blood pressure variability and left ventricular (LV) remodeling. Blood pressure (BP) and heart rate (HR) were measured by telemetry in C57BL/6 mice (n= 7) and mice deficient in the antioxidant enzyme methionine sulfoxide reductase A (MsrA) (n= 8), before and during four weeks of Ang II infusion (1000 ng/kg/min, SC). LV end-diastolic volume (EDV), ejection fraction and mass were measured by echocardiography. Subgroups of mice were administered RIL (2.5 mg/kg/day, ICV, n = 4) over the last 2 weeks of Ang II infusion. Ang II infusion increased mean BP, BP variability, cardiac and vasomotor sympathetic tone, and LVEDV/mass ratio; and decreased cardiac vagal tone and spontaneous baroreflex sensitivity (sequence technique) (P b 0.05). All measures of dysfunction were exacerbated in MsrA−/− mice. As expected, RIL decreased sympathetic tone in all mice. Remarkably, RIL completely reversed Ang II-induced hypertension, BP variability, autonomic dysregulation, and LV remodeling in C57BL/6 andMsrA−/− mice (P b 0.05). RIL also increased (normalized) LV ejection fraction and locomotor activity in Ang II-infused MsrA−/− mice (P b 0.05). We conclude that Ang II-induced hypertension, BP variability and LV remodeling are critically dependent on increased sympathetic activity. The results strongly support therapeutic targeting of the brain to inhibit sympathetic activity in hypertension. (HL14388, VA). doi:10.1016/j.autneu.2015.07.320 14.5 Brain and renal alterations following denervation of ischemic kidney in renovascular hypertension E.E. Nishi, C.T. Bergamaschi, G.N. Gomes, J.C. Perry, G.S. Lincevicius, R.R. Campos Physiology Dpt., Universidade Federal de Sao Paulo, Brazil Psychobiology Dpt., Universidade Federal de Sao Paulo, Brazil Our aim was to investigate whether renal nerves play a role in the renal injury process and modulation of AngII receptors expression in the central nuclei and kidneys in renovascular hypertension. Denervation of clipped kidney (RD: visible bundles were dissected + 10% phenol) was performed in Wistar male rats (n = 5/group) 4–5 weeks after clip implantation (gap width: 0.2 mm). Ten days after RD, blood pressure (BP) was significantly reduced in the 2 K-1C rats. AT1R and AT2R upregulation within the rostral ventrolateral medulla (RVLM) and paraventricular nucleus of the hypothalamus (PVN) in the 2 K-1C group was normalized after RD. No change in the expression of either AngII receptor was found within the nucleus of the tractus solitarius (NTS). Following RD, there was no change in plasma renin activity in control and 2 K-1C rats. In order to distinguish the effects of RD from the reduction in BP, 2 K-1C rats were treated orally with hydralazine (25 mg/kg/day for seven consecutive days). Hydralazine significantly reduced BP and AT1R within the PVN in the 2 K-1C rats, but there were no changes in AT1R or AT2R within the RVLM and NTS. Following RD, renal injury was attenuated in both ischemic and contralateral kidneys of hypertensive rats, although hydralazine decreased injury only in the contralateral kidney. These results demonstrate that the renal nerves may modulate AngII receptors within the RVLM and renal injury in the ischemic kidney independent of BP and plasma renin activity in the 2 K-1C model of arterial hypertension. Supported by FAPESP and CNPq. doi:10.1016/j.autneu.2015.07.321 Symposium 15: Sleep and autonomic nervous system: At the crossroad between health and disease 15.1 Cardiovascular alterations induced by acute paradoxical sleep deprivation in rats