RESUMO
Hypertension is an important risk factor concomitant with cardiovascular disease (CVD) states, which is why we set out to evaluate Californian red worm hydrolysates on antihypertensive activity both in vitro, ex vivo, using rabbit aortic rings and in vivo using hypertensive induced rats. The worms were manually separated, washed with water, purged for 4 h with 4 % sodium bicarbonate, sacrificed with 7 % saline, and finally washed with drinking water. The in vitro antihypertensive capacity was performed by measuring angiotensin-converting enzyme inhibition; for the ex vivo assays, rabbit aorta was used to measure relaxation; for the in vivo assays, rats with induced hypertension were used to perform acute (hypotension) and chronic assays, using captopril as a control in all assays. With respect to angiotensin-converting enzyme (ACE) inhibition, the EC50 value of the worm hydrolysate was found to be 358 ppm; with respect to the analysis in aortic rings, it was found that the mechanisms of action of the hydrolysate are endothelium-dependent, presenting a maximum relaxation of 35 %. With respect to the in vivo assays, the hypotensive test showed that the hydrolysate can reduce blood pressure by up to 32 % in only 2 h, while the chronic analysis showed that the hydrolysate at 150 ppm did not present statistically significant differences with the control (captopril) during the 15 days of analysis. The Red Californian earthworm hydrolysate presents bioactive compounds identified with antihypertensive activities in vitro, ex vivo and in vivo in different isolated and animal models. The study demonstrates the efficacy of the hydrolysate to be used as an alternative in the treatment and prevention of hypertension, and it can be implemented in functional foods or nutraceutical foods. Antihypertensive peptides, particularly those that inhibit angiotensin-converting enzyme (ACE), hold significant importance in medical research, specifically in the context of cardiovascular disease treatment, particularly hypertension. The focus on these peptides and the potential implications of their results in medical research can be summarized through several key points: 1) Mechanisms of Action-Antihypertensive peptides function by inhibiting ACE or renin, crucial enzymes in blood pressure regulation. 2)Alternatives to Synthetic Drugs, 3) Additional Health Benefits, and various other factors.
RESUMO
Background: Passiflora quadrangularis L. is among the species used in Colombian folk medicine for hypertension, but until now it has not been studied in experimental models. Objectives: To assess the capacity of P. quadrangularis L. EtOH extract to prevent the hypertension and vascular remodelling induced by nitric oxide (NO) deficit in Wistar rats. Methods: The nitric oxide (NO) synthase inhibitor L-NAME (10 mg/kg, i.p (intraperitoneal), every 48h) was administered for seven weeks to the following groups of rats: P. quadrangularis L.75, 150 and 300 mg/kg/d, p.o. (oral route); enalapril as reference agent, 10 mg/kg/d, p.o. and vehicle as control (mixture of propylene glycol 10%, glycerine 10% and polysorbate 2%). Arterial blood pressure (BP) and heart rate (HR) were measured twice a week. After sacrifice, the aortic rings were isolated, contraction was triggered with phenylephrine (PE 10-6 M) and then the relaxant response achieved with cumulative concentrations of acetylcholine (ACh, 10-10 10-5 M) or sodium nitroprusside (SNP, 10-10 10-5 M) was assessed. Histopathologic measures of thickness/lumen ratio from both the left ventricle and aorta walls, as well as phytochemical screening, were also performed. Results: As for enalapril, all doses of P. quadrangularis L. prevented the hypertension induced by L-NAME (122±1.2 versus 155±1.3 mmHg at seventh week). P. quadrangularis L. significantly increased the relaxant effect induced by ACh in isolated aorta and decreased the thickness/lumen ratio of aorta wall specimens. Conclusions: P. quadrangularis L. prevents experimental hypertension induced in rats with nitric oxide deficits improving the endothelium vasodilatation response and protecting against vascular remodelling.
Antecedentes: Passiflora quadrangularis L. es una de las especies utilizadas en medicina tradicional en Colombia para la hipertensión pero hasta el momento no se ha evaluado en modelos experimentales. Objetivos: Evaluar la capacidad del extracto etanólico de P. quadrangularis L. para prevenir la hipertensión y el remodelado vascular inducidos por déficit de óxido nítrico (NO) en ratas Wistar. Métodos: El inhibidor de la óxido nítrico (NO) sintasa L-NAME (10 mg/kg, i.p, cada 48 h) se administró durante siete semanas a los siguientes grupos de tratamiento: P. quadrangularis L. 75, 150 y 300 mg/kg/d, p.o; Enalapril como agente de referencia, 10 mg/kg/d, p.o., y vehículo como control (mezcla de propilenglicol 10%, glicerina 10% y polisorbato 2%). Se midió la presión arterial (BP) y la frecuencia cardiaca (HR) dos veces por semana. Después del sacrificio, se aislaron los anillos aórticos, se desencadenó la contracción con fenilefrina (PE 10-6 M) y la respuesta relajante con concentraciones acumulativas de acetilcolina (ACh, 10-10 10-5 M) o nitroprusiato de sodio (SNP, 10-10 10-5 M). También se realizaron estudios histopatológicos de la relación entre el espesor y el lumen tanto en el ventrículo izquierdo como en las paredes de la aorta, así como un cribado fitoquímico. Resultados: Enalapril y todas las dosis de P. quadrangularis L. evitaron la hipertensión inducida por L-NAME (122 ± 1,2 frente a 155 ± 1,3 mm Hg a la séptima semana). P. quadrangularis L. aumentó significativamente el efecto relajante inducido por ACh en la aorta aislada y disminuyó la relación entre el espesor y la luz de los especímenes en la pared de la aorta. Conclusiones: P. quadrangularis L. previene la hipertensión experimental inducida por déficit de óxido nítrico en ratas, mejorando la respuesta del endotelio y protegiendo frente al remodelado vascular.
