Central hypotensive action of clonidine requires nitric oxide.
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.
Dobrucki
L W
LW
Department of Chemistry, Ohio University, Athens, USA.
Cabrera
C L
CL
Bohr
D F
DF
Malinski
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015374:Biosensing Techniques; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology*; D004563:Electrochemistry / Q000295:instrumentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D003000:Clonidine; D019331:NG-Nitroarginine Methyl Ester