Influence of female sex hormones on endothelium-derived vasoconstrictor prostanoid generation in microvessels of spontaneously hypertensive rats

Although female sex hormones may attenuate endothelial dysfunction in spont aneously hypertensive rats (SHR) by increasing endothelium-derived relaxing factors (EDRFs), the influence of ovarian hormones on the generation of en dothelium-derived contracting factors (EDCFs) remains unknown. The aim of t his study was to evaluate the effect of estrogen and progesterone on the ge neration of vasoconstrictor prostanoids and superoxide anion (O-2(-)) by mi crovessels from SHR. Vascular reactivity to norepinephrine (NE), acetylchol ine (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 estrad iol + progesterone. The vascular reactivity was evaluated in the absence or presence of indomethacin (INDO, 10 mu mol/L) and sodium diclofenac (DIC, 1 0 mu mol/L), ridogrel (RID, 50 mu mol/L), dazoxiben (DAZ, 10 mu mol/L), or superoxide dismutase (SOD, 100 U/mL). Prostanoid levels in the arteriolar p erfusate 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 estr adiol + 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 PGF(2 alpha), but not of TXB2 and 6-keto-PGF(1 alpha), was greater in OVX-SHR than in OE-SHR micr ovessels with endothelium when stimulated by NE. This response was normaliz ed by hormonal treatments. Neither NE nor ACh stimulated prostanoid product ion by microvessels without endothelium. These results suggest that estroge n may protect female SHR against severe hypertension partly by decreasing t he synthesis of EDCFs such as PGH(2)/PGF(2 alpha) and O-2(-).