Actions of L-NAME and methylene blue on the hypotensive effects of clonidine and rilmenidine in the anesthetized rat.
The antihypertensive mechanism of alpha2-adrenoceptor agonists, such as clonidine and rilmenidine, is not completely elucidated, although it is probably due to reduction of sympathetic tone mediated by stimulation of central alpha2-adrenoceptors. Because activation of alpha2-adrenoceptors on endothelial cells induces release of endothelium-derived relaxing factor (EDRF), we determined whether nitric oxide (NO) release is involved in the antihypertensive action of clonidine and rilmenidine. In chloralose-anesthetised Wistar rats, systolic and diastolic arterial blood pressures were recorded on a polygraph. Intravenous injection of clonidine or rilmenidine (control group) caused a rapid increase of arterial blood pressure. followed by a long-lasting hypotensive effect. The hypotensive effects, estimated as the area enclosed by the decrease in diastolic pressure during the 20 min after clonidine and rilmenidine injections, were 574+/-60 and 410+/-59 mm Hg/min, respectively. The delta decrease in diastolic arterial blood pressure observed 20 min after intravenous injections of clonidine and rilmenidine was 48+/-5 and 34+/-3 mm Hg, respectively. Clonidine and rilmenidine injected 5-10 min after intravenous pretreatment with L-NAME (2 and 1 mg/kg) or methylene blue (10 mg/kg) induced hypotensive effects that were significantly smaller than that observed for the control group. These results suggest that the antihypertensive effects of clonidine and rilmenidine also may be modulated by the NO-cyclic guanosine monophosphate (cGMP) pathway at the level of the central nervous system and/or at the vascular peripheral circulation.
Soares de Moura
R S
RS
Departamento de Farmacologia IB, Centro Biomédico, Universidade do Estado do Rio de Janeiro, Brazil. demoura@uerj.br
Leão
M C
MC
Castro Resende
A C
AC
Moreira
C F
CF
Sena
K M
KM
Silveira
S S
SS
Lima
A F
AF
Nunes
F R
FR
Mesquita Ferreira
A G
AG
D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007022:Hypotension / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology / Q000627:therapeutic use*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077769:Rilmenidine
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D010080:Oxazoles; D009569:Nitric Oxide; D006152:Cyclic GMP; D003000:Clonidine; D000077769:Rilmenidine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester