Vasorelaxant effects of 1-nitro-2-phenylethane, the main constituent of the essential oil of Aniba canelilla, in superior mesenteric arteries from spontaneously hypertensive rats.

The present study investigated the mechanisms underlying the vasorelaxant effects of the essential oil of Aniba canelilla (EOAC) and its main constituent 1-nitro-2-phenylethane (NP) in isolated superior mesenteric artery from spontaneously hypertensive rats (SHRs). At 0.1-1000 µg/mL, EOAC and NP relaxed SMA preparations pre-contracted with 75 mMKCl with IC(50) (geometric mean [95% confidence interval]) values of 294.19 [158.20-94.64] and 501.27 [378.60-624.00] µg/mL, respectively); or with phenylephrine (PHE) (IC(50)s=11.07 [6.40-15.68] and 7.91 [4.08-11.74) µg/mL, respectively). All these effects were reversible and remained unaltered by vascular endothelium removal. In preparations maintained under Ca(2+)-free conditions, EOAC and NP (both at 600 µg/mL) reduced the PHE-, but not the caffeine-induced contraction. In Ca(2+)-free and high K(+) (75 mM) medium, the contractions produced by CaCl(2) or BaCl(2) were reduced or even abolished by EOAC and NP at 100 and 600 µg/mL, respectively. EOAC and NP (both at 10-1000 µg/mL) also relaxed the contraction evoked by phorbol dibutyrate (IC(50)=52.66 [10.82-94.64] and 39.13 [31.55-46.72] µg/mL, respectively). It is concluded that NP has a myogenic endothelium-independent vasorelaxant effects and appears to be the active principle of the EOAC. Vasorelaxant effect induced by both EOAC and NP is preferential to receptor-activated pathways and it appears to occur intracellularly more than a superficial action restricted to the membrane environment such as a simple blocking activity on a given receptor or ion channel.

Cardiovascular effects of 1-nitro-2-phenylethane, the main constituent of the essential oil of Aniba canelilla, in spontaneously hypertensive rats.

This study investigated the cardiovascular responses to the essential oil of Aniba canelilla (EOAC) and its main constituent 1-nitro-2-phenylethane (NP) in spontaneously hypertensive rats (SHRs). In anesthetized SHRs, intravenous (i.v.) bolus injections of EOAC (1-20 mg/kg) or NP (1-10 mg/kg) elicited dose-dependent hypotensive and bradycardiac effects, which were characterized in two periods (phases 1 and 2). The first rapid component (phase 1) evoked by EOAC and NP both at 10 mg/kg was absent after left ventricle injection, fully abolished by bilateral vagotomy and perineural treatment of both cervical vagus nerves with capsaicin (250 µg/mL) while remained unaltered by i.v. pretreatment with capsazepine (1 mg/kg) or ondansetron (30 µg/kg). In conscious SHRs, NP (5 and 10 mg/kg, i.v.) evoked rapid hypotensive and bradycardiac effects (phase 1) that were fully abolished by methylatropine (1 mg/kg, i.v.) pretreatment. In rat endothelium-containing mesenteric preparations, increasing concentrations (0.1-1000 µg/mL) of EOAC and NP relaxed the phenylephrine-induced contraction in a concentration-dependent manner. It is concluded that NP induces a vago-vagal bradycardiac and depressor reflex (phase 1) that apparently results from the stimulation of vagal pulmonary rather than cardiac C-fiber afferents. This effect does not appear to involve activation of either vanilloid TPRV(1) or 5-HT(3) receptors located on vagal sensory nerves. The phase 2 hypotensive response to i.v. NP seems to result, at least in part, from its direct vasodilatory effect on the peripheral smooth muscle. All in vivo and in vitro effects of EOAC are mostly attributed to the actions of its main constituent NP.

1-Nitro-2-phenylethane, the main constituent of the essential oil of Aniba canelilla, elicits a vago-vagal bradycardiac and depressor reflex in normotensive rats.

Previously, it was shown that intravenous (i.v.) treatment with the essential oil of Aniba canelilla (EOAC) elicited a hypotensive response that is due to active vascular relaxation rather than to the withdrawal of sympathetic tone. The present study investigated mechanisms underlying the cardiovascular responses to 1-nitro-2-phenylethane, the main constituent of the EOAC. In pentobarbital-anesthetized normotensive rats, 1-nitro-2-phenylethane (1-10mg/kg, i.v.) elicited dose-dependent hypotensive and bradycardiac effects which were characterized in two periods (phases 1 and 2). The first rapid component (phase 1) evoked by 1-nitro-2-phenylethane (10mg/kg) was fully abolished by bilateral vagotomy, perineural treatment of both cervical vagus nerves with capsaicin (250 microg/ml) and was absent after left ventricle injection. However, pretreatment with capsazepine (1mg/kg, i.v.) or ondansetron (30 microg/kg, i.v.) did not alter phase 1 of the cardiovascular responses to 1-nitro-2-phenylethane (10mg/kg, i.v.). In conscious rats, 1-nitro-2-phenylethane (1-10mg/kg, i.v.) evoked rapid hypotensive and bradycardiac (phase 1) effects that were fully abolished by methylatropine (1mg/kg, i.v.). It is concluded that 1-nitro-2-phenylethane induces a vago-vagal bradycardiac and depressor reflex (phase 1) that apparently results from the stimulation of vagal pulmonary rather than cardiac C-fiber afferents. The transduction mechanism of the 1-nitro-2-phenylethane excitation of C-fiber endings is not fully understood and does not appear to involve activation of either Vanilloid TPRV(1) or 5-HT(3) receptors. The phase 2 hypotensive response to 1-nitro-2-phenylethane seems to result, at least in part, from a direct vasodilatory effect since 1-nitro-2-phenylethane (1-300 microg/ml) induced a concentration-dependent reduction of phenylephrine-induced contraction in rat endothelium-containing aorta preparations.

Pressor responsiveness to intravenous quinpirole is blunted in malnourished, conscious rats: central vs. peripheral and spinal mechanisms.

In conscious rats, intravenous treatment with the dopamine D2-like receptor agonist quinpirole, elicited a pressor effect, which is attributed to central dopamine D2 receptor-mediated activation of sympathetic outflow associated with arginine vasopressin release. This prominent central effect is opposed to peripheral sympathoinhibitory and spinal depressor effects. The present study investigated the effects of pre- and postnatal undernutrition on the central pressor responsiveness to quinpirole. Malnourished (MalN) rats were obtained by feeding dams a multideficient diet (providing 8% protein) during pregnancy and nursing. At 90 days of age, MalN rats weighed significantly less than control (CNT) rats born to dams fed standard commercially diet (23% protein) during pregnancy and nursing. Baseline mean arterial pressure and heart rate in MalN rats were comparable to those of CNT. Intravenous treatment with quinpirole (0.3 mg/kg) in MalN conscious rats induced a pressor effect, which was significantly reduced in both magnitude and duration, when compared with CNT rats. In both groups studied, pressor response to quinpirole was fully abolished by the peripheral and central dopamine D2 receptor antagonist, metoclopramide (5 mg/kg, i.v.) whereas was significantly enhanced after pretreatment with either intravenous (0.5 mg/kg) or intrathecal (40 microg per rat at T9-T10 level) domperidone, a dopamine D2 receptor antagonist that does not cross the blood-brain barrier. However, even under peripheral and spinal dopamine D2 receptor blockade, maximum pressor effect of quinpirole remained significantly reduced in MalN when compared with CNT rats. Neither the maximum pressor nor the bradycardiac responses to intravenous phenylephrine or arginine vasopressin differed between CNT and MalN rats. This study shows that undernutrition imposed during fetal life and suckling blunted the pressor response to quinpirole in conscious rats. This blunted response appears mainly related to desensitization of brain dopamine D2 receptors rather than enhanced peripheral and/or spinal dopamine D2 receptor-mediated depressor effect or vascular hyporesponsiveness to alpha1-adrenoceptor and vasopressin receptor stimulation.

Cardiovascular effects of the essential oil of Ocimum gratissimum leaves in rats: role of the autonomic nervous system.

1. The cardiovascular effects of intravenous (i.v.) administration of the essential oil of Ocimum gratissimum (EOOG) were investigated in rats. In addition, the present study examined: (i) whether the autonomic nervous system is involved in the mediation of EOOG-induced changes in mean aortic pressure (MAP) and heart rate (HR); and (ii) whether these changes could be attributed, at least in part, to the actions of eugenol, the major constituent of EOOG. 2. In both pentobarbitone-anaesthetized and conscious rats, i.v. bolus injections of EOOG (1-20 mg/kg) elicited immediate and dose-dependent decreases in MAP and HR. These responses to EOOG were of the same order of magnitude irrespective of whether the animal was under general anaesthesia. 3. Pretreatment of anaesthetized rats with bilateral vagotomy did not significantly modify the EOOG-induced dose-dependent hypotension, whereas it significantly reduced the bradycardia at the highest dose used. 4. In conscious rats, i.v. injections of bolus doses (1-10 mg/kg) of eugenol also elicited immediate and dose-dependent decreases in MAP and HR. Intravenous pretreatment of conscious rats with either methylatropine (1 mg/kg) or hexamethonium (30 mg/kg) significantly reduced the EOOG-induced dose-dependent bradycardia without affecting the hypotension. 5. These data show, for the first time, that i.v. administration of EOOG to either anaesthetized or conscious rats induces an immediate and significant hypotension and bradycardia, which appear to be due, at least in part, to the actions of the major constituent of EOOG, eugenol. These cardiovascular effects appear to be mediated by different pathways because only EOOG-induced hypotension appears to be independent of the presence of an operational autonomic nervous system. This may suggest that the hypotensive activity of EOOG results from its vasodilatory effects directly upon vascular smooth muscle.