RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Solanum torvum fruits are commonly used in Cameroonian traditional medicine for treatment of arterial hypertension. It has been previously shown that intravenous administration of aqueous extract from dried fruits (AEST) reduced blood pressure. AIM: The present work evaluates acute toxicity and effects of oral administration of AEST in chronic arterial hypertension induced by L-NAME. Effects of AEST were also evaluated on isolated aorta. MATERIALS AND METHODS: AEST (200 mg/kg/day, p.o.) was given solely or concomitantly with L-NAME (40 mg/kg/day, p.o.) for 30 consecutive days. Animal body weight, systolic blood pressure and heart rate were measured before stating the treatment and at the end of each week. Urinary volume and urinary sodium and potassium contents were quantified before and at days 1, 15 and 30 of the treatment. Aorta from treated animals was tested for their sensitivity to noradrenaline and carbachol. Aorta from normal untreated rats was used to evaluate the in vitro vascular effect of AEST. RESULTS: The results showed that AEST did induce neither mortality nor visible signs of toxicity. When given solely or in co-administration with L-NAME, AEST significantly reduced animal's body weight. It amplified the hypertensive and cardiac hypertrophy effect of L-NAME and did not affect these parameters in normotensive animals. AEST increased the sensitivity to noradrenaline in normotensive and significantly reduced it in hypertensive animals. AEST significantly increased urinary volume and sodium excretion in L-NAME treated animals while reducing the sodium excretion in normotensive. In vitro, AEST induced a potent partial endothelium-dependent contraction of aortic ring; contractions that were partially antagonized by prazosin and verapamil and were not relaxed by carbachol. CONCLUSION: These results suggest that oral chronic administration of AEST induced potentiation of arterial hypertension and cardiac hypertrophy in L-NAME treated rats. These effects may result from a reduction in sensitivity to vasorelaxant agents and increase in hypersensitivity to contractile factors. AEST possess potent in vitro vasocontractile activity that may result from activation of both alpha(1)-adrenergic pathway and calcium influx.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Frutas/química , Hipertensión/inducido químicamente , NG-Nitroarginina Metil Éster/farmacología , Solanum/química , Animales , Aorta Torácica/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Carbacol/farmacología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/fisiopatología , Técnicas In Vitro , Indicadores y Reactivos , Riñón/efectos de los fármacos , Masculino , Ratones , Relajación Muscular/efectos de los fármacos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Norepinefrina/farmacología , Tamaño de los Órganos/efectos de los fármacos , Parasimpaticomiméticos/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Ratas , Solanum/toxicidad , Vasoconstrictores/farmacologíaRESUMEN
Hypertension induced by nitric oxide synthase inhibition is associated with functional abnormalities of the heart and kidney. The aim of the present study was to investigate whether chronic treatment with Arbutus unedo leaf (AuL) or root (AuR) aqueous extracts can prevent these alterations. Six groups of rats were used: control group received tap water; N(G)-nitro-l-arginine methyl-ester (L-NAME) group treated with L-NAME at 40 mg/kg/day; AuL and AuR groups received simultaneously L-NAME (40 mg/kg/day) and Au leaves or roots extract at the same concentration 250 mg/kg/day; l-arginine and enalapril groups received simultaneously L-NAME (40 mg/kg/day) and l-arginine at 50mg/kg/day or enalapril at 15 mg/kg/day. Treatment of rats during 4 weeks with L-NAME caused an increase of the systolic blood pressure (SBP) accompanied by a ventricular hypertrophy, an impairment of endothelium-dependent vasorelaxation, an increase of the cardiac baroreflex sensitivity and a decrease of water, sodium and potassium excretion. The co-administration of AuL or AuR extracts with L-NAME reduces the development of increased SBP, ameliorates the vascular reactivity as well as the baroreflex sensitivity and normalizes the renal function. AuR reduces the ventricular hypertrophy but AuL do not. Enalapril associated with L-NAME reverses the majority of alterations induced by L-NAME while l-arginine only lightly ameliorates the vascular reactivity. These results show that chronic treatment with Arbutus extract regress the development of hypertension and ameliorate cardiovascular and renal functions in NO deficient hypertension.