Document Detail

Central hypotensive action of clonidine requires nitric oxide.
MedLine Citation:
PMID:  11602488     Owner:  NLM     Status:  MEDLINE    
Background- Clonidine has an antihypertensive effect by its action in the brain and, because we observed that the tonic production of nitric oxide (NO) in the brain is required to maintain blood pressure at its low, normotensive level, the current study was designed to determine whether the hypotensive action of clonidine resulted from its stimulation of excess NO in the brain. Methods and Results- Porphyritic microsensors were used to quantify NO concentration in the nucleus tractus solitarius (NTS) in vitro in brain slices and in vivo in the anesthetized rat. In both preparations, the basal production of NO in the NTS was 15+/-3 nmol/L. In vitro stimulation of the NTS with clonidine (50 nmol/L) resulted in an increase in the NO concentration to 84+/-7 nmol/L. In vivo, the intracerebroventricular (ICV) infusion of clonidine (0.03 microgram) caused an increase in NO concentration in the NTS to 128+/-17 nmol/L. This ICV injection of clonidine caused a fall in mean arterial pressure of -22+/-1 mm Hg and a decrease of heart rate of -18+/-2%. The blockade of NO production with N(G)-nitro-L-arginine-methyl ester (2 micromol; delivered ICV, 30 minutes before the clonidine) reduced responses to clonidine for both mean arterial pressure and heart rate (-3+/-1 mm Hg and -2+/-1% change, respectively). Conclusion- The stimulation of the release of NO in the brain by clonidine contributes to its central antihypertensive action.
L W Dobrucki; C L Cabrera; D F Bohr; T Malinski
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  104     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-16     Completed Date:  2001-12-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1884-6     Citation Subset:  AIM; IM    
Department of Chemistry, Ohio University, Athens, USA.
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MeSH Terms
Antihypertensive Agents / pharmacology*
Biosensing Techniques
Blood Pressure / drug effects
Brain / drug effects*,  metabolism*
Clonidine / pharmacology*
Electrochemistry / instrumentation
Enzyme Inhibitors / pharmacology
Heart Rate / drug effects
Injections, Intraventricular
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / analysis,  metabolism*
Nitric Oxide Synthase / antagonists & inhibitors
Rats, Sprague-Dawley
Solitary Nucleus / drug effects,  metabolism
Grant Support
Reg. No./Substance:
0/Antihypertensive Agents; 0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 4205-90-7/Clonidine; 50903-99-6/NG-Nitroarginine Methyl Ester; EC Oxide Synthase

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