Central blockade of nitric oxide synthesis reduces moxonidine-induced hypotension.
1. Nitric oxide (NO) and alpha(2)-adrenoceptor and imidazoline agonists such as moxonidine may act centrally to inhibit sympathetic activity and decrease arterial pressure. 2. In the present study, we investigated the effects of pretreatment with l-NAME (NO synthesis inhibitor), injected into the 4th ventricle (4th V) or intravenously (i.v.), on the hypotension, bradycardia and vasodilatation induced by moxonidine injected into the 4th V in normotensive rats. 3. Male Wistar rats with a stainless steel cannula implanted into the 4th V and anaesthetized with urethane were used. Blood flows were recorded by use of miniature pulsed Doppler flow probes implanted around the renal, superior mesenteric and low abdominal aorta. 4. Moxonidine (20 nmol), injected into the 4th V, reduced the mean arterial pressure (-42+/-3 mmHg), heart rate (-22+/-7 bpm) and renal (-62+/-15%), mesenteric (-41+/-8%) and hindquarter (-50+/-8%) vascular resistances. 5. Pretreatment with l-NAME (10 nmol into the 4th V) almost abolished central moxonidine-induced hypotension (-10+/-3 mmHg) and renal (-10+/-4%), mesenteric (-11+/-4%) and hindquarter (-13+/-6%) vascular resistance reduction, but did not affect the bradycardia (-18+/-8 bpm). 6. The results indicate that central NO mechanisms are involved in the vasodilatation and hypotension, but not in the bradycardia, induced by central moxonidine in normotensive rats.
Moreira
Thiago Santos
TS
Department of Physiology, Universidade Federal de Sao Paulo - Escola Paulista de Medicina, 04023-060, Sao Paulo, SP, Brazil.
Takakura
Ana Carolina Thomaz
AC
Menani
José V
JV
Sato
Monica Akemi
MA
Colombari
Eduardo
E
D000818:Animals; D001919:Bradycardia / Q000139:chemically induced; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism*; D001938:Brazil; D004338:Drug Combinations; D018619:Echocardiography, Doppler, Pulsed / Q000379:methods; D020546:Fourth Ventricle / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced* / Q000517:prevention & control*; D007093:Imidazoles / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000493:pharmacokinetics; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004338:Drug Combinations; D007093:Imidazoles; D009569:Nitric Oxide; C043482:moxonidine; D019331:NG-Nitroarginine Methyl Ester