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Effect of gender on cardiovascular responses to orthostatic stress – a modeling approach

Women are more predisposed to orthostatic intolerance than men. The mechanisms for this difference to orthostatic challenges may involve reduced neural sympathetic activation and/or lower blood volume in women. We used the Female and Male models developed under the Quantitative Human Physiology model to investigate these mechanisms. The female model was scaled based on current data in terms of plasma volume, organ and body structure and hemodynamics. The Female and the Male were subjected to head‐up tilt (HUT) of 60deg for 6 min and cardiovascular variables monitored continuously by time‐dependent iterations. The data were compared with published studies (Am.J.Physiol.Regul.Integr.Comp 289:R109‐116) where an identical protocol was used in men and women. We found that the increase in blood pressure was lower (1 vs. 5 mmHg) and the decrease in SV more pronounced (‐4 vs. ‐1 mL) in the Female vs. the Male, paralleling the changes observed in the human study. Cerebral perfusion was decreased more severely in the Female despite similar sympathetic outflow responses to orthostatic challenge. The absolute volume of blood sequestered in the veins of the lower torso region of the model was similar in the Female and Male, but % of total blood volume (9% vs. 6%) was higher in the Female. Since estrogens may increase the sensitivity of the baroreflex (BRS), we modeled the response to HUT during a 2‐fold increase in BRS in both the Male and Female. While the cardiovascular dynamics were improved in the Male, the Female had a more severe decrease in SV (‐6 mL), despite increased sympathetic outflow. The results of the model and the experimental data suggest that cardiovascular compensatory responses in women during orthostatic challenges are impaired primarily due to lower overall blood volume than in men. Supported by HL 51971, and a NSF EPSCoR.