Il6 and Acute Pressor Response to Psychological Stress

Project: Research project

Description

We have new data showing marked tachycardic and hypertensive responses in male mice switched to cages previously occupied by a different male mouse. The pressor, but not the heart rate or activity, effect of this stress is blunted significantly in interleukin-6 (IL-6) knockout mice. We also have new evidence that shows considerable acute and chronic interaction with the sympathetic and renin-angiotensin systems. This project will test the hypothesis that interleukin-6 (IL-6) plays a major role in sympathetic- and angiotensin II-mediated hypertensive responses to psychosocial stress. The Specific Aims are:
1) to test the hypothesis that IL-6 contributes significantly to the acute pressor response to psychological stress. We will use acute cage-switch stress testing in mice to determine whether
a) IL-6 knockout (KO) mice have a blunted increase in blood pressure compared to wild-type (WT) mice; b) TNF-a knockout mice have an attenuated pressor response to cage switch, similar to IL-6 knockout;
c) restoring IL-6 in KO mice will restore a normal pressor response to psychological stress;
d) the pressor response in WT mice injected with IL-6 antibody will mimic the response in IL-6 KO mice.
2) to determine the role of IL-6 in mediating the bi-directional blood pressure interactions between acute psychosocial stress and chronic hypertension. These experiments will determine whether:
a) cage-switch stress causes IL-6-dependent hypertension after the initial pressor response has subsided;
b) Angll hypertension increases the dependence of psychosocial stress-induced pressor responses on IL-6;
c) repeated cage-switch stress testing causes a greater increase in MAP over time in WT versus KO mice.
3) to test the hypothesis that the sympathetic nervous system initiates IL-6-dependent blood pressure increases during acute stress, directly and through stimulation of the renin-angiotensin system. We will study the blood pressure increase during acute cage-switch stress testing and test the hypotheses that:
a) a-/b-adrenergic receptor blockade will block the pressor response more in WT than in IL-6 KO mice;
b) Angll receptor blockade will block the pressor response more in WT compared to IL-6 KO mice;
c) the effect of adrenergic blockade will be blunted in mice with the Angll system clamped at normal.
StatusFinished
Effective start/end date4/1/044/30/10

Funding

  • National Institutes of Health: $2,129,352.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $2,135,829.00
  • National Institutes of Health: $2,133,275.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $2,068,401.00
  • National Institutes of Health
  • National Institutes of Health: $2,078,758.00
  • National Institutes of Health

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Angiotensin II
rho-Associated Kinases
Hypertension
Blood Vessels
Blood Pressure
Cytokines
Interleukin-6
Vasoconstriction
Superoxides
Muscle Cells
Contractile Proteins
Research
Arachidonic Acid
Knockout Mice
Biochemistry
Signal Transduction
Endothelium
Reactive Oxygen Species
Animal Models
Research Personnel

ASJC

  • Medicine(all)