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Endothelial‐Derived ET‐1 Contributes to the Pressor Response Elicited by Acute Behavioral Stress
Author(s) -
Fox Brandon M,
Loria Analia S,
Hyndman Kelly A,
Johns Robin,
Jin Chunhua,
Pollock David M,
Yanagisawa Masashi,
Pollock Jennifer S
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.964.10
Subject(s) - blood pressure , medicine , endocrinology , heart rate , mean arterial pressure , pressor response , endothelin 1 , endothelin receptor , receptor
Acute behavioral stress mediates a physiological acute pressor response. In both humans and animal models, acute behavioral stress induces increased circulating endothelin‐1 (ET‐1) levels. However, the functional consequences of elevated plasma ET‐1 as well as the cellular source of the ET‐1 are unknown. We hypothesized that acute behavioral stress induces endothelial‐derived ET‐1 mediating, in part, the acute pressor response. We utilized vascular endothelial‐specific ET‐1 knockout (VEETKO) and flox control mice for all experiments. VEETKO mice demonstrated significantly reduced aortic and renal vascular preproET‐1 mRNA compared with flox mice (1.0 ± 0.2 vs. 0.03 ± 0.01 A.U. and 1.0 ± 0.2 vs. 0.3 ± 0.1 A.U. respectively, p<0.05). Adult male mice were exposed to cage switch stress (CSS), an established model of acute behavioral stress. Plasma ET‐1 was significantly elevated in control mice in response to CSS (0.92 ± 0.04 vs. 1.2 ± 0.08 pg/ml, p<0.05), whereas CSS did not elicit an increase in plasma ET‐1 in VEETKO mice (0.52 ± 0.09 vs. 0.63 ± 0.08 pg/ml, p>0.05). Blood pressure, heart rate, and activity were measured by radiotelemetry in conscious freely moving mice. CSS induced an acute pressor response in both VEETKO and control mice, however, the pressor response was significantly blunted in VEETKO mice ( Fig 1; mean arterial pressure, p<0.05, systolic, p<0.05, and diastolic pressure, p<0.05). No difference in the CSS induced response was observed for pulse pressure, heart rate, or activity. Importantly, VEETKO and flox mice showed a similar reduction in adrenal norepinephrine (NE) content in response to CSS. ET receptor expression profiles were similar in both genotypes, indicating no difference in ET‐1 clearance capacity between groups. These results indicate that acute behavioral stress induces endothelial‐derived ET‐1 that contributes to the acute pressor response. These findings suggest a novel mechanism of neuro‐endothelial cross talk that contributes to the physiological pressor response to behavioral stress. Support or Funding Information This work was supported by funding from the National Institutes of Health ‐ P01 HL095499 and P01 HL069999 to Dr. Jennifer Pollock and Dr. David Pollock, F30 DK107194 to Brandon Fox, and partially supported by MSTP T32 GM008361. 1Blood pressure response to CSS in VEETKO and flox control mice. A) Mean arterial pressure, B) Systolic pressure, and C) Diastolic pressure. Statistics represent 2‐way repeated measures ANOVA. VEETKO mice display a significantly blunted pressor response to CSS compared to flox control mice.