CNS neuroplasticity and salt-sensitive hypertension induced by prior treatment with subpressor doses of ANG II or aldosterone.
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.
Department of Psychology, University of Iowa, Iowa City, Iowa;
Sarah C
SC
Clayton
Department of Psychology, University of Iowa, Iowa City, Iowa; Nanyang Institute of Technology, Zhang Zhongjing College of Chinese Medicine, Henan, China.
Zhongming
Z
Zhang
Department of Psychology, University of Iowa, Iowa City, Iowa;
Terry
T
Beltz
Department of Psychology, University of Iowa, Iowa City, Iowa;
Baojian
B
Xue
Department of Psychology, University of Iowa, Iowa City, Iowa; Department of Health and Human Physiology, University of Iowa, Iowa City, Iowa; Department of Pharmacology, University of Iowa, Iowa City, Iowa; Cardiovascular Center, University of Iowa, Iowa City, Iowa; and alan-johnson@uiowa.edu.
Alan Kim
AK
Johnson
D000450:Aldosterone / Q000009:adverse effects*; D000804:Angiotensin II / Q000009:adverse effects*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002490:Central Nervous System / Q000503:physiopathology*; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018738:Hexamethonium / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000959:Antihypertensive Agents; D019208:Brain-Derived Neurotrophic Factor; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D018738:Hexamethonium; D000450:Aldosterone; D000242:Cyclic AMP; D048051:p38 Mitogen-Activated Protein Kinases
aldosterone; angiotensin II; neuroplasticity; salt sensitivity; sensitization