Male-Female Differences in Upregulation of Vasoconstrictor Responses in Human Cerebral Arteries

Background and purpose: Male-female differences may significantly impact stroke prevention and treatment in men women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which is associated with lower flow. The present study investigates if cerebral arteries from men and women differ in cerebrovascular upregulation. Experimental approach: Freshly obtained human cerebral arteries were placed in organ culture, an established model studying receptor upregulation. 5-hydroxtryptamine type 1B (5-HT1B), angiotensin II type 1 (AT(1)) and endothelin-1 type and B (ETA and ETB) receptors were evaluated using wire myograph for contractile responses, real-time PCR for mRNA immunohistochemistry for receptor expression. Key results: Vascular sensitivity to angiotensin II and endothelin-1 was markedly lower in cultured cerebral arteries women as compared to men. ETB receptor-mediated contraction occurred in male but not female arteries. there were similar upregulation in mRNA and expression of 5-HT1B, AT(1), and E-TB receptors and in local expression of Ang II after organ culture. Conclusions and Implications: In spite of receptor upregulation after organ culture in both sexes, cerebral arteries women were significantly less responsive to vasoconstrictors angiotensin II and endothelin-1 as compared to arteries men. This suggests receptor coupling and/or signal transduction mechanisms involved in cerebrovascular contractility be suppressed in females. This is the first study to demonstrate sex differences in the vascular function of human arteries.