Sexual dimorphism in the effect of nonhabituating stress on neurogenic plasma extravasation

Abstract

The sympathoadrenal axis contributes to the sexual dimorphism of the inflammatory response. As stress both activates the sympathoadrenal axis and profoundly affects inflammation and inflammatory disease, we evaluated whether stress exerts a sexually dimorphic effect on a major component of the inflammatory response, plasma extravasation. We evaluated the effect of a nonhabituating stress, repeated intermittent sound (30 min ⁄ day for 4 days), on neurogenic synovial plasma extravasation, induced by bradykinin in the rat knee joint. Sound stress profoundly inhibited bradykinin-induced plasma extravasation in male rats, but profoundly enhanced it in female rats. These effects took 24 h to fully develop after the last exposure to stress. In gonadectomized males, bradykinin-induced plasma extravasation was lower than intact males, and sound stress now enhanced it, i.e. gonadectomized males were phenotypically like intact females. In gonadectomized females, bradykinin-induced plasma extravasation was greater than in intact adult females, and sound stress still enhanced it. Adrenal enucleation significantly attenuated the effect of sound stress on bradykinin-induced plasma extravasation in both male and female rats. We tested the hypothesis that these effects of sound stress were due to sustained enhanced plasma levels of stress hormones. Corticosterone and epinephrine, only when administered in combination, over five days, produced a qualitatively similar effect as sound stress, i.e. bradykinin-induced plasma extravasation was significantly decreased in males and increased in females. These findings suggest that a combined effect of the hypothalamic-pituitary adrenal and sympathoadrenal stress axes are responsible for the marked sexual dimorphism in the effect of stress on the inflammatory response.

Sympathoadrenal‐dependent sexually dimorphic effect of nonhabituating stress on in vivo neutrophil recruitment in the rat

“…While the relationship between stress and inflammation is well established (see Black (2002) for a review), the influence of sex on stress‐induced effects on inflammation has received little attention despite the fact that stressful events are known to produce sexually dimorphic effects on the immune system, for example, men have an increased risk of major infections following trauma (Offner et al ., 1999). We have shown that the sympathoadrenal axis modulates a major component of the inflammatory response (plasma extravasation) in a sexual dimorphic manner (Green et al ., 1999) and we have also shown that activation of the sympathoadrenal axis by nonhabituating stress inhibits plasma extravasation in male rats, while enhancing it in females (Green & Levine, 2005). In this study, we tested the hypothesis that neutrophils, which are the primary initial defense against bacterial infection, exhibit a sexually dimorphic chemotactic response in reaction to a nonhabituating chronic stress, and that this effect is mediated by the sympathoadrenal axis.…”

Vascular Endothelial Cells Mediate Mechanical Stimulation-Induced Enhancement of Endothelin Hyperalgesia via Activation of P2X2/3Receptors on Nociceptors

“…Plasma extravasation was evaluated as described previously (Green and Levine, 2005). Rats were anesthetized with sodium pentobarbital (65 mg/kg, intraperitoneal) and were then given a tail vein injection of Evans blue dye (50 mg/kg), which binds stoichiometrically to serum albumin.…”

β2-Adrenergic receptor-dependent sexual dimorphism for murine leukocyte migration

“…With the greater involvement of other leukocytes, such as macrophages and monocytes in chronic inflammatory conditions it is possible that there could be a contribution of α-adrenergic receptors in modulating leukocyte function. Of note, estradiol decreases platelet α 2 -adrenergic receptors number and function (Brodde, 1983;Mishra et al, 1985), and the role of sex steroids in inflammation, which we have previously investigated in other models (Barker et al, 2005;Green et al, 2001;Green et al, 1999a;Green and Levine, 2005) is also an important question. However, to establish any sex steroid contribution to adrenergic mechanisms in leukocyte recruitment, at minimum we would need to perform male and female gonadectomy, sex steroid replacement with testosterone and dihydrotestosterone (to determine the contribution of estradiol) in males, and estradiol and progesterone in females.…”