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

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

Hypertension (Dallas, Tex. 1979), 2001-09, Vol.38 (3, Part 2 Suppl), p.692-696 [Periódico revisado por pares]

Philadelphia, PA: American Heart Association, Inc

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Título:
Ovarian Hormones Modulate Endothelin-1 Vascular Reactivity and mRNA Expression in DOCA-Salt Hypertensive Rats
Autor: David, Flavia L ; Carvalho, Maria Helena C ; Cobra, Ana L.N ; Nigro, Dorothy ; Fortes, Zuleica B ; Rebouças, Nancy A ; Tostes, Rita C.A
Assuntos: Animals ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Pressure - drug effects ; Body Weight - drug effects ; Cardiology. Vascular system ; Desoxycorticosterone - administration & dosage ; Endothelin-1 - genetics ; Endothelin-1 - pharmacology ; Endothelins - pharmacology ; Estradiol - blood ; Estradiol - pharmacology ; Experimental diseases ; Female ; Hypertension - chemically induced ; Hypertension - genetics ; Hypertension - physiopathology ; In Vitro Techniques ; Medical sciences ; Mesenteric Arteries - drug effects ; Mesenteric Arteries - metabolism ; Mesenteric Arteries - physiology ; Organ Size - drug effects ; Ovariectomy ; Peptide Fragments - pharmacology ; Potassium, Dietary - administration & dosage ; Progesterone - blood ; Progesterone - pharmacology ; Rats ; Rats, Wistar ; Receptor, Endothelin A ; Receptor, Endothelin B ; Receptors, Endothelin - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - drug effects ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Sodium Chloride, Dietary - administration & dosage ; Time Factors ; Uterus - growth & development ; Vasoconstriction - drug effects
É parte de: Hypertension (Dallas, Tex. 1979), 2001-09, Vol.38 (3, Part 2 Suppl), p.692-696
Descrição: 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,Ala]-ET-1(8-21) (IRL-1620), an ETB agonist. Mechanisms underlying these gender differences are unclear, and we hypothesized that the ovarian hormones attenuate vascular ETB responses in female DOCA-salt rats. Female Wistar rats were randomized in 3 groupssham-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 ETA/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 ETB receptor mRNA levels were greatly enhanced in OVX-DOCA but not OVX-control rats. Hormone replacement with E or EP restored ETB receptor expression in the DOCA group. A greater blood pressure–lowering effect of bosentan (ETA/ETB blocker) was observed in OVX-DOCA rats. The observation that OVX worsens hypertension as well as the altered ETB receptor–mediated responses and the effects of bosentan in female DOCA rats supports our suggestion that the ovarian hormones modulate ET-1/ETB receptor vascular responses/expression in DOCA-salt hypertension.
Editor: Philadelphia, PA: American Heart Association, Inc
Idioma: Inglês

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

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

Philadelphia, PA: American Heart Association, Inc

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