Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Lund, Sweden.
PLoS One. 2013 Apr 29;8(4):e62698. doi: 10.1371/journal.pone.0062698. Print 2013.
Male-female differences may significantly impact stroke prevention and treatment in men and women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found in males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which is associated with lower blood flow. The present study investigates if cerebral arteries from men and women differ in cerebrovascular receptor upregulation.
Freshly obtained human cerebral arteries were placed in organ culture, an established model for studying receptor upregulation. 5-hydroxtryptamine type 1B (5-HT1B), angiotensin II type 1 (AT1) and endothelin-1 type A and B (ETA and ETB) receptors were evaluated using wire myograph for contractile responses, real-time PCR for mRNA and immunohistochemistry for receptor expression.
Vascular sensitivity to angiotensin II and endothelin-1 was markedly lower in cultured cerebral arteries from women as compared to men. ETB receptor-mediated contraction occurred in male but not female arteries. Interestingly, there were similar upregulation in mRNA and expression of 5-HT1B, AT1, and ETB receptors and in local expression of Ang II after organ culture.
In spite of receptor upregulation after organ culture in both sexes, cerebral arteries from women were significantly less responsive to vasoconstrictors angiotensin II and endothelin-1 as compared to arteries from men. This suggests receptor coupling and/or signal transduction mechanisms involved in cerebrovascular contractility may be suppressed in females. This is the first study to demonstrate sex differences in the vascular function of human brain arteries.
男性和女性之间的差异可能会显著影响男女中风的预防和治疗，但对于中风性别二态性的潜在机制仍不清楚。我们之前在男性中发现，脑缺血会上调脑动脉中的收缩受体，从而导致脑血流量降低。本研究旨在探讨男性和女性的脑动脉在脑血管受体上调方面是否存在差异。
新鲜获取的人脑动脉置于器官培养中，这是一种研究受体上调的成熟模型。使用线描记法评估 5-羟色胺 1B 型（5-HT1B）、血管紧张素 II 型 1（AT1）和内皮素 1 型 A 和 B（ETA 和 ETB）受体的收缩反应，实时 PCR 评估 mRNA 水平，免疫组织化学评估受体表达。
与男性相比，女性培养后的脑动脉对血管紧张素 II 和内皮素-1 的敏感性明显降低。ETB 受体介导的收缩仅发生在男性动脉中，而女性动脉中则没有。有趣的是，在器官培养后，5-HT1B、AT1 和 ETB 受体的 mRNA 和表达以及 Ang II 的局部表达在两性中均有类似的上调。
尽管在两性的器官培养后都有受体上调，但与男性相比，女性脑动脉对血管收缩剂血管紧张素 II 和内皮素-1 的反应明显减弱。这表明参与脑血管收缩的受体偶联和/或信号转导机制可能在女性中受到抑制。这是首次证明人类脑动脉血管功能存在性别差异的研究。
