Effects of age and sex on cerebrovascular function in the rat middle cerebral artery

被引:8
作者
Deer, Rachel R. [2 ,3 ]
Stallone, John N. [1 ,2 ]
机构
[1] Texas A&M Univ, Michael E DeBakey Inst, Womens Hlth Div, College Stn, TX 77843 USA
[2] Texas A&M Univ, Dept Vet Physiol & Pharmacol, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA
[3] Univ Texas Med Branch, Sealy Ctr Aging, Galveston, TX 77550 USA
来源
BIOLOGY OF SEX DIFFERENCES | 2014年 / 5卷
基金
美国国家卫生研究院;
关键词
Cerebrovascular; Sex-differences; Vasoconstriction; Sexual dimorphism; Cyclooxygenase; Thromboxane; VASOPRESSIN-INDUCED CONTRACTION; VASCULAR SMOOTH-MUSCLE; NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; ENDOTHELIAL DYSFUNCTION; PROSTACYCLIN SYNTHASE; GENE-EXPRESSION; MYOGENIC TONE; BLOOD-VESSELS; ESTROGEN;
D O I
10.1186/s13293-014-0012-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 M) or COX-2 (NS398, NS, 10 mu M). VP-stimulated release of PGI(2) and TXA(2) were measured using radioimmunoassay of 6-keto-PGF(1 alpha) 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 PGI(2) or TXA(2) 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 PGI(2) and TXA(2) 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 PGI(2) and TXA(2) 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.
引用
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页数:10
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共 44 条
  • [1] 17β-estradiol differentially regulates blood-brain barrier permeability in young and aging female rats
    Bake, S
    Sohrabji, F
    [J]. ENDOCRINOLOGY, 2004, 145 (12) : 5471 - 5475
  • [2] The effect of the menstrual cycle on human cerebral blood flow: studies using Doppler ultrasound
    Brackley, KJ
    Ramsay, MM
    Pipkin, FB
    Rubin, PC
    [J]. ULTRASOUND IN OBSTETRICS & GYNECOLOGY, 1999, 14 (01) : 52 - 57
  • [3] A longitudinal study of maternal bloodflow in normal pregnancy and the puerperium: analysis of Doppler waveforms using Laplace transform techniques
    Brackley, KJ
    Ramsay, MM
    Pipkin, FB
    Rubin, PC
    [J]. BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 1998, 105 (01): : 68 - 77
  • [4] AGING IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION IN HEALTHY-MEN YEARS BEFORE THE AGE-RELATED DECLINE IN WOMEN
    CELERMAJER, DS
    SORENSEN, KE
    SPIEGELHALTER, DJ
    GEORGAKOPOULOS, D
    ROBINSON, J
    DEANFIELD, JE
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1994, 24 (02) : 471 - 476
  • [5] Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function
    Csiszar, A
    Ungvari, Z
    Edwards, JG
    Kaminski, P
    Wolin, MS
    Koller, A
    Kaley, G
    [J]. CIRCULATION RESEARCH, 2002, 90 (11) : 1159 - 1166
  • [6] Cerebrovascular effects of oestrogen: Multiplicity of action
    Duckles, Sue P.
    Krause, Diana N.
    [J]. CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2007, 34 (08): : 801 - 808
  • [7] The vascular protective effects of estrogen
    Farhat, MY
    Lavigne, MC
    Ramwell, PW
    [J]. FASEB JOURNAL, 1996, 10 (05) : 615 - 624
  • [8] Sexual dimorphism in prostanoid-potentiated vascular contraction: roles of endothelium and ovarian steroids
    Fulton, CT
    Stallone, JN
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2002, 283 (05): : H2062 - H2073
  • [9] ENDOTHELIUM-DEPENDENT CONTRACTIONS ARE ASSOCIATED WITH BOTH AUGMENTED EXPRESSION OF PROSTAGLANDIN-H SYNTHASE-1 AND HYPERSENSITIVITY TO PROSTAGLANDIN H-2 IN THE SHR AORTA
    GE, T
    HUGHES, H
    JUNQUERO, DC
    WU, KK
    VANHOUTTE, PM
    BOULANGER, CM
    [J]. CIRCULATION RESEARCH, 1995, 76 (06) : 1003 - 1010
  • [10] Estrogen reduces mouse cerebral artery tone through endothelial NOS- and cyclooxygenase-dependent mechanisms
    Geary, GG
    Krause, DN
    Duckles, SP
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2000, 279 (02): : H511 - H519