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(Hypertension. 1999;34:914-919.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Influence of Female Sex Hormones on Endothelium-Derived Vasoconstrictor Prostanoid Generation in Microvessels of Spontaneously Hypertensive Rats

Ana Paula V. Dantas; Regina Scivoletto; Zuleica B. Fortes; Dorothy Nigro; Maria Helena C. Carvalho

From the Laboratory of Hypertension, Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, Brazil.

Correspondence to Maria Helena C. Carvalho, Laboratory of Hypertension, Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, 05508-900, Av Prof Lineu Prestes, 1524, São Paulo, SP, Brazil. E-mail mahecaca{at}.icb.usp.br

Abstract—Although female sex hormones may attenuate endothelial dysfunction in spontaneously hypertensive rats (SHR) by increasing endothelium-derived relaxing factors (EDRFs), the influence of ovarian hormones on the generation of endothelium-derived contracting factors (EDCFs) remains unknown. The aim of this study was to evaluate the effect of estrogen and progesterone on the generation of vasoconstrictor prostanoids and superoxide anion (O₂^-) by microvessels from SHR. Vascular reactivity to norepinephrine (NE), acetylcholine (ACh), and sodium nitroprusside (SNP) were evaluated in the mesenteric arteriolar bed from estrous (OE) and ovariectomized (OVX) SHR. OVX-SHR were treated for 24 hours or 15 days with estradiol and for 15 days with estradiol+progesterone. The vascular reactivity was evaluated in the absence or presence of indomethacin (INDO, 10 µmol/L) and sodium diclofenac (DIC, 10 µmol/L), ridogrel (RID, 50 µmol/L), dazoxiben (DAZ, 10 µmol/L), or superoxide dismutase (SOD, 100 U/mL). Prostanoid levels in the arteriolar perfusate of mesenteries with or without endothelium were measured by enzyme immunoassay. An increased reactivity to NE and reduced sensitivity to ACh were observed in microvessels from OVX-SHR compared with OE-SHR. There were no differences in the responses to SNP. Treatments with estradiol and estradiol+progesterone similarly restored these altered responses. INDO, DIC, RID, and SOD also restored the NE and ACh responses in OVX-SHR. DAZ had no effect on the vascular reactivities. The release of PGF₂, but not of TXB₂ and 6-keto-PGF₁, was greater in OVX-SHR than in OE-SHR microvessels with endothelium when stimulated by NE. This response was normalized by hormonal treatments. Neither NE nor ACh stimulated prostanoid production by microvessels without endothelium. These results suggest that estrogen may protect female SHR against severe hypertension partly by decreasing the synthesis of EDCFs such as PGH₂/PGF₂ and O₂^-.

Key Words: estrogen • progesterone • SHR • endothelium-derived contracting factors • prostanoids • superoxide

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