Abstract 658: Pressor And Sympathetic Response To 2% Saline Augmented By Prior Treatment With Intracerebroventricular (icv) Angiotensin II (ANGII)
Previous studies from our laboratory demonstrate that the sensitizing effects of sub-pressor ANGII or aldosterone treatments on ANGII-induced hypertension are mediated through the CNS. The present study tested if pressor response sensitization extends to another hypertensive challenge, 2% saline given as the sole drinking fluid. The study followed an Induction-Delay-Expression (I-D-E) experimental design. We instrumented rats with telemetry devices to continuously record blood pressure (BP) and heart rate throughout the experiments. After one week recovery and one week baseline (B) recording, rats underwent a second surgery to implant icv cannulas to continuously deliver ANGII (1 ng/kg/min; prior ANGII) or vehicle (control) for one week (I). After I and after a 1 week D, drinking water was switched to 2% saline (E). The degree of autonomic tone was assessed via ganglionic blockade (hexamethonium, 30 mg/kg, ip) during B, after I, and during E. During B, group BPs were not different (103±2 mmHg control vs. 107±4mmHg, prior-ANGII). Although drinking only 2% saline increased BPs in both groups (122±3 mmHg, control vs. 141±9 mmHg, prior-ANGII), the absolute increase was greater in rats treated with ANGII during I (19±3, control vs. 34±6, prior-ANGII, p<0.05). At B, control and prior-ANGII treated rats showed no difference in the depressor response to hexamethonium (-17±3%, control vs. -13±1%, prior-ANGII) or after I (-13±5%, control vs. -20±9%, prior-ANGII). However, during E while drinking2% saline, prior-ANGII treated rats displayed a significantly larger fall in BP to hexamethonium than controls (-20±5%, control vs. -36±7%, prior-ANGII, p<0.05), suggesting that during E a higher degree of sympathetic tone maintained BP in the prior-ANGII treated rats. These data show that icv treatment with ANGII sensitizes the hypertensive response induced by 2% saline intake and that this enhanced pressor effect is accompanied by elevated sympathetic tone. These results provide new insights into the etiology of salt-sensitive hypertension by implicating a role for ANGII-induced neuroplasticity in CNS systems controlling sympathetic tone.
- © 2012 by American Heart Association, Inc.