title: Effects of age and sex on cerebrovascular function in the rat middle cerebral artery.
abstract: BACKGROUND
  Although the mechanisms underlying the beneficial effects of estrogen on cerebrovascular function are well known, the age-dependent deleterious effects of estrogen are largely unstudied. It was hypothesized that age and sex interact in modulating cerebrovascular reactivity to vasopressin (VP) by altering the role of prostanoids in vascular function.
  
  
  METHODS
  Female (F) Sprague-Dawley rats approximating key stages of "hormonal aging" in humans were studied: premenopausal (mature multigravid, MA, cyclic, 5-6 months) and postmenopausal (reproductively senescent, RS, acyclic, 10-12 months). Age-matched male (M) rats were also studied. Reactivity to VP (10(-12)-10(-7) M) was measured in pressurized middle cerebral artery segments in the absence or presence of selective inhibitors of COX-1 (SC560, SC, 1 μM) or COX-2 (NS398, NS, 10 μM). VP-stimulated release of PGI2 and TXA2 were measured using radioimmunoassay of 6-keto-PGF1α and TXB2 (stable metabolites, pg/mg dry wt/45 min).
  
  
  RESULTS
  In M, there were no changes in VP-induced vasoconstriction with age. Further, there were no significant differences in basal or in low- or high-VP-stimulated PGI2 or TXA2 production in younger or older M. In contrast, there were marked differences in cerebrovascular reactivity and prostanoid release with advancing age in F. Older RS F exhibited reduced maximal constrictor responses to VP, which can be attributed to enhanced COX-1 derived dilator prostanoids. VP-induced vasoconstriction in younger MA F utilized both COX-1 and COX-2 derived constrictor prostanoids. Further, VP-stimulated PGI2 and TXA2 production was enhanced by endogenous estrogen and decreased with advancing age in F, but not in M rats.
  
  
  CONCLUSIONS
  This is the first study to examine the effects of age and sex on the mechanisms underlying cerebrovascular reactivity to VP. Interestingly, VP-mediated constriction was reduced by age in F, but was unchanged in M rats. Additionally, it was observed that selective blockade of COX-1 or COX-2 produced age-dependent changes in cerebrovascular reactivity to VP and that VP-stimulated PGI2 and TXA2 production were enhanced by endogenous estrogen in younger F. A better understanding of the mechanisms by which estrogen exerts its effects may lead to new age- and sex-specific therapeutic agents for the prevention and/or treatment of cerebrovascular diseases.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A & M University, College Station 77843-4466, TX, USA ; Sealy Center on Aging, University of Texas Medical Branch, 301 University Boulevard, Galveston 77550-0177, TX, USA.
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Deer
authors.affiliation: Women's Health Division, Michael E. DeBakey Institute, Texas A & M University, College Station 77843-4466, TX, USA ; Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A & M University, College Station 77843-4466, TX, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Stallone
keywords: Cerebrovascular; Cyclooxygenase; Sex-differences; Sexual dimorphism; Thromboxane; Vasoconstriction