17-beta estradiol independently regulates erythropoietin synthesis and NOS activity during hypoxia.
We reported previously that 17-beta estradiol (E2-beta) attenuates hypoxic induction of erythropoietin (EPO) synthesis in rats. We hypothesized this attenuation is mediated by increased nitric oxide (NO) bio-availability. To investigate this hypothesis, ovariectomized estrogen-depleted rats were instrumented with arterial and venous catheters and treated with either E2-beta (20 microg/24 hrs) or vehicle (polypropylene glycol) for 7 days. Rats were placed in Plexiglas boxes and administered a bolus of either the NO synthase inhibitor, Nomega-nitro-L-arginine (l-NNA, 15 mg/kg) or saline. Following this bolus, saline or l-NNA was continuously infused (15 mg/kg/h) throughout the 8 hours of hypoxic exposure (12% O2). Hypoxia increased plasma NO metabolites (NOx) in both saline groups but more in E2-beta-treated rats. l-NNA prevented this increase in both groups. Renal endothelial NO synthase (NOS) expression was unaltered by hypoxia, l-NNA, or E2-beta. Despite preventing increases in plasma NOx during hypoxia, l-NNA did not affect E2-beta attenuation of EPO synthesis. We conclude that E2-beta independently attenuates hypoxic induction of EPO and augments hypoxic increases in NO synthesis.
Mukundan
Harshini
H
Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico, Health Sciences Center Albuquerque, New Mexico 87131, USA.
Resta
Thomas C
TC
Kanagy
Nancy L
NL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004921:Erythropoietin / Q000096:biosynthesis* / Q000097:blood; D004958:Estradiol / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D004921:Erythropoietin; D019335:Nitroarginine; D009569:Nitric Oxide; D004958:Estradiol; D019001:Nitric Oxide Synthase