Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 299, Issue 1, Pages R185-R191Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00333.2009
Keywords
early life stress; maternal separation; air jet stress; blood pressure; endothelin; corticosterone
Categories
Funding
- National Institutes of Health [P01 HL 69999]
- American Heart Association
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Loria AS, D'Angelo G, Pollock DM, Pollock JS. Early life stress downregulates endothelin receptor expression and enhances acute stress-mediated blood pressure responses in adult rats. Am J Physiol Regul Integr Comp Physiol 299: R185-R191, 2010. First published April 21, 2010; doi:10.1152/ajpregu.00333.2009.-We hypothesized that early life stress enhances endothelin (ET-1)-dependent acute stress responses in adulthood. We utilized a unique rat model, wildtype (WT) and ETB receptor-deficient spotting lethal (sl/sl) rats, as well as pharmacological blockade of ET receptors, in a model of early life stress, maternal separation (MS). MS was performed in male WT and sl/sl rats 3 h/day from day 2 to 14 of life. Acute air jet stress (AJS)-induced responses (elevation in blood pressure, plasma corticosterone, and plasma ET-1) were evaluated in adult MS rats compared with the nonhandled littermate (control) rats. MS significantly augmented the acute AJS-induced blood pressure response (area under the curve) in WT rats compared with control, while the AJS-induced pressor responses were similar in sl/sl MS and control rats. ET receptor blockade significantly blunted the AJS- induced pressor response in WT MS and control rats. Moreover, AJS- induced plasma corticosterone levels in control rats were sensitive to ET receptor blockade, yet, AJS did not alter plasma corticosterone levels in MS rats. MS significantly increased circulating ET-1 levels, and AJS- induced plasma ET-1 levels were similarly increased in control and MS rats. MS induced a significant downregulation in expression of ETA and ETB receptors in aortic tissue compared with control rats. These results indicate that early life stress reduced expression of ETA and ETB receptors, leading to alterations in the ET pathway, and an exaggerated acute stress-mediated pressor response in adulthood.
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