Endogenous testosterone increases leukocyte-endothelial cell interaction in spontaneously hypertensive rats

Area of Science:

• Cardiovascular Physiology
• Immunology
• Endocrinology

Background:

• Inflammation plays a key role in cardiovascular disease development and progression.
• Testosterone influences vascular function, which is often impaired in arterial hypertension.
• Spontaneously hypertensive rats (SHR) exhibit altered vascular characteristics relevant to cardiovascular disease.

Purpose of the Study:

• To investigate the impact of endogenous testosterone on leukocyte behavior in mesenteric venules of SHR.
• To determine if testosterone modulates leukocyte-endothelial cell interactions in the context of hypertension.

Main Methods:

• Utilized 18-week-old intact SHR, castrated SHR, and normotensive Wistar rats.
• Measured blood pressure via tail plethysmography and serum testosterone levels using ELISA.
• Assessed leukocyte rolling, adhesion, and migration in vivo using intravital microscopy.

Main Results:

• Castration of SHR significantly reduced blood pressure and reversed elevated leukocyte rolling and adhesion.
• SHR showed increased P-selectin and ICAM-1 protein expression in mesenteric venules compared to Wistar rats.
• Testosterone depletion in SHR normalized the expression of these cell adhesion molecules.

Conclusions:

• Endogenous testosterone critically mediates hypertension-induced increases in leukocyte-endothelial cell interactions.
• Elevated expression of cell adhesion molecules contributes to testosterone's pro-inflammatory effects in SHR.
• Targeting testosterone may offer a therapeutic strategy for managing vascular inflammation in hypertension.