title: Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Lund, Sweden. hilda.ahnstedt@med.lu.se
authors: Hilda
authors: H
authors: Ahnstedt
authors: Lei
authors: L
authors: Cao
authors: Diana N
authors: DN
authors: Krause
authors: Karin
authors: K
authors: Warfvinge
authors: Hans
authors: H
authors: Säveland
authors: Ola G
authors: OG
authors: Nilsson
authors: Lars
authors: L
authors: Edvinsson
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009213:Myography; D009924:Organ Culture Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D020033:Protein Isoforms; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A; D044302:Receptor, Serotonin, 5-HT1B; D000804:Angiotensin II
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