Rita de C V de A F Da Silva1, Priscila de Souza1, Sandra Crestani1, Arquimedes Gasparotto Júnior2, Aline A Boligon3, Margareth L Athayde3, José Eduardo da Silva-Santos4. 1. Department of Pharmacology, Universidade Federal do Paraná, Curitiba, PR, Brazil. 2. Faculty of Health Sciences, Universidade Federal da Grande Dourados, Dourados, MS, Brazil. 3. Department of Industrial Pharmacy, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. 4. Department of Pharmacology, Universidade Federal do Paraná, Curitiba, PR, Brazil; Laboratory of Cardiovascular Pharmacology, Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: j.e.silva.santos@ufsc.br.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Scutia buxifolia, a native tree popularly known as "coronilha", is widely used in Brazilian folk medicine for diuretic and anti-hypertensive purposes. AIM OF THE STUDY: We investigated the effects of a butanolic (BuOH) soluble fraction of the hydroethanolic extract (HESB) of bark of Scutia buxifolia on both blood pressure and urinary excretion of rats. The involvement of the nitric oxide/guanylate cyclase pathway in the hypotensive effect found was also explored. MATERIAL AND METHODS: We tested the effect of the BuOH soluble fraction of HESB on the mean arterial pressure (MAP) of anesthetized rats. The fraction was administered at doses of 1, 3 and 10mg/kg (i.v.) in normotensive rats during continuous infusion of vehicle (10 μl/min), or phenylephrine (4 μg/kg/min), or l-NAME (7 mg/kg/min), two approaches able to induce a sustained hypertensive state. In some experiments, a bolus injection of ODQ (2mg/kg) was administered in animals infused with phenylephrine before the administration of the BuOH soluble fraction of HESB. We also measured the effects of the BuOH soluble fraction on the MAP of spontaneously hypertensive rats (SHR). Separate groups of rats were treated orally with either HESB (10, 30 or 100mg/kg), or its BuOH soluble fraction (3, 10 or 30 mg/kg), and were subjected to measurement of diuresis and blood pressure. RESULTS: The BuOH soluble fraction of HESB (10mg/kg, i.v.) reduced the MAP of both phenylephrine-infused and SHR rats by 20.6 ± 6.0 and 41.8 ± 8.3 mm Hg, respectively. However, no hypotensive effect was found in normotensive animals infused with l-NAME, a non-selective inhibitor of nitric oxide synthase, or animals previously treated with the soluble guanylate cyclase inhibitor ODQ. The urinary excretion was increased by 70% at 6-8h after a single oral administration of the BuOH soluble fraction of HESB (10mg/kg), without change in urinary density, pH, or Na(+) and K(+) concentrations. In addition, MAP was lower 3h after the acute oral treatment with the BuOH soluble fraction (82.1 ± 3.8 mm Hg), compared with MAP of animals from the control group (97 ± 3.2 mm Hg). CONCLUSION: This study demonstrates that the BuOH soluble fraction of the hydroethanolic bark of Scutia buxifolia, which has its bark used in folk medicine for the treatment of hypertension mainly by its presumed diuretic properties, possesses both diuretic and hypotensive effects in rats, and that at least the hypotensive effect is fully dependent on activation of the nitric oxide/guanylate cyclase pathway.
ETHNOPHARMACOLOGICAL RELEVANCE: Scutia buxifolia, a native tree popularly known as "coronilha", is widely used in Brazilian folk medicine for diuretic and anti-hypertensive purposes. AIM OF THE STUDY: We investigated the effects of a butanolic (BuOH) soluble fraction of the hydroethanolic extract (HESB) of bark of Scutia buxifolia on both blood pressure and urinary excretion of rats. The involvement of the nitric oxide/guanylate cyclase pathway in the hypotensive effect found was also explored. MATERIAL AND METHODS: We tested the effect of the BuOH soluble fraction of HESB on the mean arterial pressure (MAP) of anesthetized rats. The fraction was administered at doses of 1, 3 and 10mg/kg (i.v.) in normotensive rats during continuous infusion of vehicle (10 μl/min), or phenylephrine (4 μg/kg/min), or l-NAME (7 mg/kg/min), two approaches able to induce a sustained hypertensive state. In some experiments, a bolus injection of ODQ (2mg/kg) was administered in animals infused with phenylephrine before the administration of the BuOH soluble fraction of HESB. We also measured the effects of the BuOH soluble fraction on the MAP of spontaneously hypertensiverats (SHR). Separate groups of rats were treated orally with either HESB (10, 30 or 100mg/kg), or its BuOH soluble fraction (3, 10 or 30 mg/kg), and were subjected to measurement of diuresis and blood pressure. RESULTS: The BuOH soluble fraction of HESB (10mg/kg, i.v.) reduced the MAP of both phenylephrine-infused and SHR rats by 20.6 ± 6.0 and 41.8 ± 8.3 mm Hg, respectively. However, no hypotensive effect was found in normotensive animals infused with l-NAME, a non-selective inhibitor of nitric oxide synthase, or animals previously treated with the soluble guanylate cyclase inhibitor ODQ. The urinary excretion was increased by 70% at 6-8h after a single oral administration of the BuOH soluble fraction of HESB (10mg/kg), without change in urinary density, pH, or Na(+) and K(+) concentrations. In addition, MAP was lower 3h after the acute oral treatment with the BuOH soluble fraction (82.1 ± 3.8 mm Hg), compared with MAP of animals from the control group (97 ± 3.2 mm Hg). CONCLUSION: This study demonstrates that the BuOH soluble fraction of the hydroethanolic bark of Scutia buxifolia, which has its bark used in folk medicine for the treatment of hypertension mainly by its presumed diuretic properties, possesses both diuretic and hypotensive effects in rats, and that at least the hypotensive effect is fully dependent on activation of the nitric oxide/guanylate cyclase pathway.