Cardiovascular effects of intravenous (i.v.) treatment with the
essential oil of the bark of Aniba canelilla (EOAC) were investigated in normotensive rats. In both
pentobarbital-anesthetized and conscious rats, i.v. bolus
injections of EOAC (1 to 20 mg/kg) elicited similar and dose-dependent
hypotension and
bradycardia. Pretreatment of anesthetized rats with bilateral
vagotomy significantly reduced the
bradycardia without affecting the
hypotension. In conscious rats, pretreatment with
hexamethonium (30 mg/kg, i.v.) significantly reduced the EOAC-induced
bradycardia without affecting the
hypotension. The opposite effect was observed after i.v. pretreatment with the
nitric oxide synthase inhibitor, N-nitro-
L-arginine methyl esther (
L-NAME, 20 mg/kg). However, both EOAC-
induced hypotension and
bradycardia were significantly reduced by pretreatment with
methylatropine (1 mg/kg, i.v.). In rat endothelium-containing aorta preparations, EOAC (1-600 microg/mL) induced a concentration-dependent reduction of
potassium (60 mM)-induced contraction [IC50 (geometric mean+/-95% confidence interval)=64.5 (45.6-91.2) microg/mL)], an effect that was significantly reduced by the addition of
atropine (10 microM) in the perfusion medium [IC50=109.5 (72.5-165.4) microg/mL)]. Furthermore, the
vasorelaxant effects of the EOAC were also but significantly reduced [IC50=139.1 (105.2-183.9) microg/mL)] by removal of the vascular endothelium. Furthermore, the CaCl2-induced contractions in
calcium-free medium were reduced and even fully abolished by EOAC (100 and 600 microg/mL), respectively. However, EOAC (600 microg/mL) was without significant effect on
caffeine-induced contractions in
calcium-free medium. These data show that i.v. treatment of rats with EOAC induces dose-dependent
hypotension and
bradycardia, which occurred independently. The
bradycardia appears mainly dependent upon the presence of an operational and functional parasympathetic drive to the heart. However, the
hypotension is due to an active vascular relaxation rather than withdrawal of sympathetic tone. This relaxation seems partly mediated by an endothelial
L-arginine/
nitric oxide pathway through peripheral
muscarinic receptor activation (endothelium-dependent relaxation) and predominantly through an inhibition of
calcium inward current (endothelium-independent relaxation).