Estrogen-dependent enhancement of NO production in the nucleus tractus solitarius contributes to ethanol-induced hypotension in conscious female rats.
BACKGROUND
Our previous pharmacological and cellular studies showed that peripheral (cardiac and vascular) nitric oxide synthase (NOS)-derived NO is implicated in the estrogen (E(2))-dependent hypotensive action of ethanol in female rats. The objective of this study was to test the hypothesis that enhanced NO production in the nucleus tractus solitarius (NTS) is implicated in the E(2)-dependent hypotensive action of ethanol.


METHODS
To achieve this goal, we utilized in vivo electrochemistry to measure real time changes in neuronal NO to investigate the acute effects of intragastric ethanol (0, 0.5, or 1 g/kg) on NO in NTS neurons, blood pressure (BP), and heart rate (HR) in conscious female rats in the absence (ovariectomized, OVX, rats) or presence of E(2).


RESULTS
In sham operated (SO) rats, ethanol elicited dose-related increase in NTS NO and reduction in BP. These neurochemical and BP effects of ethanol were absent in OVX rats. Whether the neurochemical effect of ethanol and the associated hypotension are dependent on rapid E(2) signaling was investigated. In OVX rats pretreated, 30 minutes earlier, with E(2) (1 microg/kg), intragastric ethanol (1 g/kg) increased NTS NO and reduced BP and these responses were comparable to those obtained in SO rats.


CONCLUSIONS
The present findings suggest that increased production of NO in NTS neurons contributes to ethanol-evoked hypotension in female rats. Further, ethanol enhancement of neuronal NO production in the brainstem is dependent on rapid E(2) signaling.
Li
Guichu
G
Department of Pharmacology and Toxicology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Abdel-Rahman
Abdel A
AA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002138:Calibration; D002404:Catheterization; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004563:Electrochemistry; D004567:Electrodes, Implanted; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology*; D007441:Intubation, Gastrointestinal; D009569:Nitric Oxide / Q000096:biosynthesis*; D010052:Ovariectomy; D011359:Proestrus / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*
D002492:Central Nervous System Depressants; D004967:Estrogens; D009569:Nitric Oxide; D000431:Ethanol; D004958:Estradiol