CNS neuroplasticity and salt-sensitive hypertension induced by prior treatment with subpressor doses of ANG II or aldosterone

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2014-06, Vol.306 (12), p.R908-R917
• Main Authors: Clayton, Sarah C, Zhang, Zhongming, Beltz, Terry, Xue, Baojian, Johnson, Alan Kim
• Format: Article
• Language: English
• Subjects: Aldosterone - adverse effects; Angiotensin II - adverse effects; Animals; Antihypertensive Agents - pharmacology; Blood Pressure - drug effects; Blood Pressure - physiology; Brain - metabolism; Brain-Derived Neurotrophic Factor - metabolism; Central Nervous System - physiopathology; Cyclic AMP - metabolism; Disease Models, Animal; Dose-Response Relationship, Drug; Fluid and Electrolyte Homeostasis; Hexamethonium - pharmacology; Hormones; Hypertension - chemically induced; Hypertension - physiopathology; Male; Neural Control; Neurology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; p38 Mitogen-Activated Protein Kinases - metabolism; Peptides; Physiology; Rats; Rats, Sprague-Dawley; Salt; Sodium Chloride, Dietary - adverse effects
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00010.2014

Although sensitivity to high dietary NaCl is regarded to be a risk factor for cardiovascular disease, the causes of salt-sensitive hypertension remain elusive. Previously, we have shown that rats pretreated with subpressor doses of either ANG II or aldosterone (Aldo) show sensitized hypertensive responses to a mild pressor dose of ANG II when tested after an intervening delay. The current studies investigated whether such treatments will induce salt sensitivity. In studies employing an induction-delay-expression experimental design, male rats were instrumented for chronic mean arterial pressure (MAP) recording. In separate experiments, ANG II, Aldo, or vehicle was delivered either subcutaneously or intracerebroventricularly during the induction. There were no sustained differences in BP during the delay prior to being given 2% saline. While consuming 2% saline during the expression, both ANG II- and Aldo-pretreated rats showed significantly greater hypertension. When hexamethonium was used to assess autonomic control of MAP, no differences in the decrease of MAP in response to ganglionic blockade were detected during the induction. However, during the expression, the fall was greater in sensitized rats. In separate experiments, brain tissue that was collected at the end of delay showed increases in message or activation of putative markers of neuroplasticity (i.e., brain-derived neurotrophic factor, p38 mitogen-activated protein kinase, and cAMP response element-binding protein). These experiments demonstrate that prior administration of nonpressor doses of either ANG II or Aldo will induce salt sensitivity. Collectively, our findings indicate that treatment with subpressor doses of ANG II and Aldo initiate central neuroplastic changes that are involved in hypertension of different etiologies.