Cardiovascular effects induced by reticuline in normotensive rats.
The cardiovascular effects of reticuline, isolated in a pure form from the stem of Ocotea duckei Vattimo, were studied in rats by using a combined in vivo and in vitro approach. In normotensive rats, reticuline (5, 10 and 20 mg/kg, i. v., randomly) injections produced an intense hypotension. This hypotensive response was attenuated after either, L-NAME (20 mg/kg, i. v.), a nitric oxide (NO) synthase inhibitor, or atropine (2 mg/kg, i. v.), a muscarinic receptor antagonist. In isolated rat aortic rings with intact endothelium, reticuline (3 x 10 ( - 6), 3 x 10 ( - 5), 3 x 10 ( - 4), 9 x 10 ( - 4) and 1.5 x 10 ( - 3) M) inhibited in a concentration-dependent manner the contractions induced by phenylephrine (1 microM), KCl (80 mM) and KCl (30 mM), [IC (50) = (0.4 +/- 0.1, 2.4 +/- 0.4 and 3 +/- 0.4) x 10 ( - 4) M, respectively). The effect of reticuline on phenylephrine-induced contractions was attenuated by removal of the vascular endothelium [IC (50) = (2.5 +/- 0.7) x 10 ( - 4) M]. Similar results were obtained after pretreatment of the rings with L-NAME 100 microM [IC (50) = (1.3 +/- 0.1) x 10 ( - 4) M], L-NAME 300 microM [IC (50) = (3 +/- 0.3) x 10 ( - 4) M] or atropine 1 microM [IC (50) = (1.2 +/- 0.2) x 10 ( - 4) M]. On the other hand, the effect of reticuline on phenylephrine-induced contractions was not affected by indomethacin 1 microM [IC (50) = (0.7 +/- 0.3) x 10 ( - 4) M]. Reticuline (3 x 10 ( - 6), 3 x 10 ( - 5), 3 x 10 ( - 4), 9 x 10 ( - 4) and 1.5 x 10 ( - 3) M) antagonized CaCl (2)-induced contractions, and also inhibited the intracellular calcium dependent transient contractions induced by norepinephrine (1 microM), but not those induced by caffeine (20 mM). These results suggest that the hypotensive effect of reticuline is probably due to a peripheral vasodilation in consequence of: 1) muscarinic stimulation and NOS activation in the vascular endothelium, 2) voltage-dependent Ca (2+) channel blockade and/or 3) inhibition of Ca (2+) release from norepinephrine-sensitive intracellular stores.
Dias
Katy Lísias
KL
Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, João Pessoa-PB, Brazil.
Da Silva Dias
Celidarque
C
Barbosa-Filho
José Maria
JM
Almeida
Reinaldo Nóbrega
RN
De Azevedo Correia
Nadja
N
Medeiros
Isac Almeida
IA
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001011:Aorta / Q000187:drug effects; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D007262:Infusions, Intravenous; D020128:Inhibitory Concentration 50; D009119:Muscle Contraction / Q000187:drug effects*; D027444:Ocotea; D010656:Phenylephrine; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018547:Plant Stems; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000470:Alkaloids; D044182:Benzylisoquinolines; D010936:Plant Extracts; D014665:Vasodilator Agents; D010656:Phenylephrine; C003298:reticuline