Sex-specific acute effect of estrogen on endothelium-derived contracting factor in the renal artery of hypertensive Dahl rats.
OBJECTIVE
To determine whether estrogen rapidly affects endothelium-derived contracting factor (EDCF) in the renal artery of hypertensive Dahl rats, and whether factors other than nitric oxide (NO) contribute to the effect of estrogen.


METHODS
Acute effects of estrogen on the acetylcholine-induced vasomotor responses and on prostaglandin H2/thromboxane A2 mimetic, U46619,-induced contraction were examined in isolated arterial rings.


RESULTS
Dahl salt-sensitive male and female rats were fed an 8% NaCl diet for 4 weeks. The blood pressure increased more rapidly and to a greater extent in males than in females. Renal arterial rings were prepared for isometric tension recording. 17beta-Estradiol, but not the biologically less active stereoisomer, 17alpha-estradiol, improved the relaxation response to acetylcholine in renal arteries from females. Estrogen also rapidly decreased the contraction evoked by acetylcholine (10(-6) to approximately 10(-4) mol/l) in renal arteries from females and it was effective at a physiological concentration (10(-9) mol/l) in the presence of Nomega-nitro-l-arginine methyl ester (an NO synthase inhibitor). The estrogen receptor antagonist, ICI 182,780, abolished the effect of estrogen, whereas the cytochrome P450 inhibitor, miconazole, had no effect. The contraction induced by U46619 was also suppressed by estrogen, without any contribution from NO. Estrogen had no effect on either relaxation or contraction responses in renal arteries from males.


CONCLUSIONS
17beta-Estradiol antagonizes increases in vascular tone in hypertensive females by enhancing NO-dependent relaxation, and by suppressing EDCF-mediated mechanisms in an NO-independent manner.
Zhang
Ling
L
The Second Department of Physiology, Kagawa Medical University, Kagawa 761-0793, Japan.
Kosaka
Hiroaki
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006977:Hypertension, Renal; D007564:Japan; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D020303:Rats, Inbred Dahl; D012077:Renal Artery / Q000737:chemistry / Q000187:drug effects; D012737:Sex Factors; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D016232:Endothelins; D004967:Estrogens; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004958:Estradiol; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine