The roles of sensitization and neuroplasticity in the long-term regulation of blood pressure and hypertension.
After decades of investigation, the causes of essential hypertension remain obscure. The contribution of the nervous system has been excluded by some on the basis that baroreceptor mechanisms maintain blood pressure only over the short term. However, this point of view ignores one of the most powerful contributions of the brain in maintaining biological fitness-specifically, the ability to promote adaptation of behavioral and physiological responses to cope with new challenges and maintain this new capacity through processes involving neuroplasticity. We present a body of recent findings demonstrating that prior, short-term challenges can induce persistent changes in the central nervous system to result in an enhanced blood pressure response to hypertension-eliciting stimuli. This sensitized hypertensinogenic state is maintained in the absence of the inducing stimuli, and it is accompanied by sustained upregulation of components of the brain renin-angiotensin-aldosterone system and other molecular changes recognized to be associated with central nervous system neuroplasticity. Although the heritability of hypertension is high, it is becoming increasingly clear that factors beyond just genes contribute to the etiology of this disease. Life experiences and attendant changes in cellular and molecular components in the neural network controlling sympathetic tone can enhance the hypertensive response to recurrent, sustained, or new stressors. Although the epigenetic mechanisms that allow the brain to be reprogrammed in the face of challenges to cardiovascular homeostasis can be adaptive, this capacity can also be maladaptive under conditions present in different evolutionary eras or ontogenetic periods.
Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, Iowa; Department of Health and Human Physiology, The University of Iowa, Iowa City, Iowa; Department of Pharmacology, The University of Iowa, Iowa City, Iowa; François M. Abboud Cardiovascular Center, The University of Iowa, Iowa City, Iowa; and alan-johnson@uiowa.edu.
Alan Kim
AK
Johnson
Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, Iowa; Nanyang Institute of Technology, Zhang Zhongjing College of Chinese Medicine, Nanyang, Henan Province, China.
Zhongming
Z
Zhang
Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, Iowa;
Sarah C
SC
Clayton
Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, Iowa;
Terry G
TG
Beltz
Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, Iowa;
Seth W
SW
Hurley
Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, Iowa; François M. Abboud Cardiovascular Center, The University of Iowa, Iowa City, Iowa; and.
Robert L
RL
Thunhorst
Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, Iowa; François M. Abboud Cardiovascular Center, The University of Iowa, Iowa City, Iowa; and.
Baojian
B
Xue
D000222:Adaptation, Physiological; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D002319:Cardiovascular System / Q000294:innervation*; D002490:Central Nervous System / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009473:Neuronal Plasticity; D012084:Renin-Angiotensin System; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors
D000804:Angiotensin II; D000450:Aldosterone
aldosterone; cross-sensitization; induction-delay-expression paradigm; neural networks controlling blood pressure; renin-angiotensin-aldosterone systems; salt sensitivity; slow pressor angiotensin-elicited hypertension