This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by David, F. L. Articles by Tostes, R. C.A. Search for Related Content PubMed PubMed Citation Articles by David, F. L. Articles by Tostes, R. C.A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL PROGESTERONE Medline Plus Health Information High Blood Pressure Related Collections Animal models of human disease

(Hypertension. 2001;38:692.)
© 2001 American Heart Association, Inc.

Endocrine Systems

Ovarian Hormones Modulate Endothelin-1 Vascular Reactivity and mRNA Expression in DOCA-Salt Hypertensive Rats

Flavia L. David; Maria Helena C. Carvalho; Ana L.N. Cobra; Dorothy Nigro; Zuleica B. Fortes; Nancy A. Rebouças; Rita C.A. Tostes

Departments of Pharmacology (F.L.D., M.H.C.C., A.L.N.C., D.N., Z.B.F, R.C.A.T.) and Physiology (N.A.R.), Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, SP, Brazil

Correspondence to Rita C.A.Tostes, University of Sao Paulo, Institute of Biomedical Science, Pharmacology Dept, Av. Lineu Prestes, 1524 Sao Paulo, SP 05508-900 Brazil. E-mail rtostes{at}usp.br

Abstract

Abstract—— We previously demonstrated a differential activation of the endothelin-1 (ET-1) pathway in male and female deoxycorticosterone (DOCA)-salt hypertensive rats, with the male rats exhibiting marked alterations in vascular and pressor responses to ET-1 and Suc-[Glu,⁹Ala^11,15]-ET-1(8-21) (IRL-1620), an ET_B agonist. Mechanisms underlying these gender differences are unclear, and we hypothesized that the ovarian hormones attenuate vascular ET_B responses in female DOCA-salt rats. Female Wistar rats were randomized in 3 groups: sham-operated, ovariectomized (OVX), and OVX plus hormone replacement with estradiol (E) or estradiol/progesterone (EP). Two weeks later, rats were uninephrectomized and further randomized in DOCA-salt (subcutaneous injections of desoxycorticosterone and drinking water containing NaCl/KCl) and control normotensive (subcutaneous injections of vehicle and tap water). Blood pressure was evaluated both by direct and standard tail-cuff methods. Responses to IRL-1620 were evaluated in vivo/in situ in the mesenteric microcirculation. mRNA expression of ET-1 and ET_A/B receptors was evaluated in mesenteric arteries by reverse transcription–polymerase chain reaction and expressed relative to GAPDH. OVX-DOCA rats developed a more severe form of hypertension than did DOCA rats. Treatment with E or EP restored blood pressure to levels observed in DOCA rats. In the mesentery, IRL-1620 induced vasodilatation in control rats, a mild vasoconstriction in DOCA rats, and marked vasoconstriction in OVX-DOCA rats. Both E and EP decreased IRL-1620–induced vasoconstriction in the DOCA group. In the normotensive group, OVX did not change blood pressure or IRL-1620–induced vasodilation. Removal of the ovaries increased ET-1 mRNA in arteries from DOCA and control rats, although treatment with E or EP reversed these changes. Vascular ET_B receptor mRNA levels were greatly enhanced in OVX-DOCA but not OVX-control rats. Hormone replacement with E or EP restored ET_B receptor expression in the DOCA group. A greater blood pressure–lowering effect of bosentan (ET_A/ET_B blocker) was observed in OVX-DOCA rats. The observation that OVX worsens hypertension as well as the altered ET_B receptor–mediated responses and the effects of bosentan in female DOCA rats supports our suggestion that the ovarian hormones modulate ET-1/ET_B receptor vascular responses/expression in DOCA-salt hypertension.

Key Words: deoxycorticosterone • vasoconstriction • endothelin • estrogen • receptors, endothelin

This article has been cited by other articles:

				M. P. Kunert, M. R. Dwinell, I. Drenjancevic Peric, and J. H. Lombard Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SS x BN cross Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R516 - R527. [Abstract] [Full Text] [PDF]

				Md. S. Bhuiyan, N. Shioda, and K. Fukunaga Ovariectomy augments pressure overload-induced hypertrophy associated with changes in Akt and nitric oxide synthase signaling pathways in female rats Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1606 - E1614. [Abstract] [Full Text] [PDF]

				B. A. Parker, S. L. Smithmyer, J. A. Pelberg, A. D. Mishkin, M. D. Herr, and D. N. Proctor Sex differences in leg vasodilation during graded knee extensor exercise in young adults J Appl Physiol, November 1, 2007; 103(5): 1583 - 1591. [Abstract] [Full Text] [PDF]

				R. A. Khalil Sex Hormones as Potential Modulators of Vascular Function in Hypertension Hypertension, August 1, 2005; 46(2): 249 - 254. [Abstract] [Full Text] [PDF]

				J. F. Reckelhoff Sex Steroids, Cardiovascular Disease, and Hypertension: Unanswered Questions and Some Speculations Hypertension, February 1, 2005; 45(2): 170 - 174. [Full Text] [PDF]

				L. L. Yanes, D. G. Romero, V. E. Cucchiarelli, L. A. Fortepiani, C. E. Gomez-Sanchez, F. Santacruz, and J. F. Reckelhoff Role of endothelin in mediating postmenopausal hypertension in a rat model Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2005; 288(1): R229 - R233. [Abstract] [Full Text] [PDF]

				J. M. Orshal and R. A. Khalil Gender, sex hormones, and vascular tone Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R233 - R249. [Abstract] [Full Text] [PDF]