Effect of rosmarinic acid on the arterial blood pressure in normotensive and hypertensive rats: Role of ACE.

BACKGROUND: In recent years, it has been demonstrated the inhibitory effect of some plant species on the angiotensin-converting enzyme and rosmarinic acid is a prominent constituent of these species. HYPOTHESIS/PURPOSE: This study was carried out to verify the effect of rosmarinic acid on blood pressure through inhibitory activity on angiotensin-converting enzyme in rats. STUDY DESIGN: The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The potential inhibitory rosmarinic acid effect on angiotensin-converting enzyme activity was compared with captopril actions by analyzing in vivo blood pressure dose-response curves to angiotensin I and bradykinin. The in vitro plasma angiotensin-converting enzyme activity was measured by fluorimetry using the substrate Abz-FRK(Dnp)P-OH substrate. In addition, dosages of nitrite/nítrate analysis were carried out. RESULTS: (1) rosmarinic acid caused systolic blood pressure dose-dependent decrease in hypertensive rats; (2) The angiotensin I dose-response curves demonstrated that rosmarinic acid promotes minor changes in systolic blood pressure only in the hypertensive group; (3) The bradykinin dose-response curves showed that both rosmarinic acid and captopril promoted a systolic blood pressure reduction, but only the captopril effect was significant; (4) The angiotensin-converting enzyme activity in rat lung tissue was inhibited by the rosmarinic acid in a dose dependent manner; (5) The analysis of nitrite/nítrate plasma concentrations showed no significant difference among the experimental groups. CONCLUSION: The rosmarinic acid is effective in reducing blood pressure, selectively, only in hypertensive animals. The rosmarinic acid (173µM) promoted almost a 98.96% reduction on angiotensin-converting enzyme activity.

The lignan (-)-cubebin inhibits vascular contraction and induces relaxation via nitric oxide activation in isolated rat aorta.

Cubebin, the most abundant lignan in Piper cubeba, has been described as having several effects as trypanocidal, antimycobacterial, antispasmodic, antimicrobial, anti-inflammatory, and analgesic. This study investigated the vasorelaxant effect produced by (-)-cubebin in isolated rat aortic rings pre-contracted with phenylephrine (Phe), and the possible mechanism involved in this event was evaluated. Endothelium-dependent relaxation was evoked by acetylcholine and (-)-cubebin in intact aortic rings, while endothelium-independent vasorelaxation was elicited by sodium nitroprusside and (-)-cubebin in denuded rings. Cumulative concentration-response curves for Phe (10(-10) -10(-5) M) were determined for endothelium-intact and endothelium-denuded aortic rings in either the presence or absence of (-)-cubebin. Dose-response curves were also constructed for pre-incubation of vascular rings with Nω-nitro-L-arginine methyl ester (L-NAME) (a non-specific nitric oxide synthase inhibitor), indomethacin (an unspecific cyclooxygenase inhibitor), and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) (a guanylyl cyclase inhibitor). (-)-Cubebin was found to exert a vasorelaxant effect irrespective of the presence of endothelium, which was abolished by pretreatment with L-NAME and ODQ, but not with indomethacin. In addition, (-)-cubebin was able to reduce Phe contraction in the case of intact rings. These results suggest that (-)-cubebin promotes vasorelaxation via NO/cGMP pathway in rat aorta, without prostacyclin involvement.

Is rosmarinic acid underestimated as an experimental cardiovascular drug?

PURPOSE: The rationale of the present review is to analize the activity of Rosmarinus officinalis in the the cardiovascular system METHODS: A MEDLINE database search (from January 1970 to December 2011) using only rosmarinic acid as searched term. RESULTS: The references search revealed 509 references about rosmarinic acid in 40 years (the first reference is from 1970). There is a powerful prevalence of antioxidant and cancer studies. Other diseases are few cited, as inflammation, brain (Alzheimer and Parkinson disease) and, memory; allergy; diabetes; atherosclerosis, and; hypertension. It is necessary to consider the complete absence of studies on coronary artery disease, myocardial ischemia, heart failure or ischemia/reperfusion injury. CONCLUSION: Rosmarinic acid is underestimated as an experimental cardiovascular drug and deserves more attention.

Does rosmarinic acid underestimate as an experimental cardiovascular drug? / Seria o ácido rosmarínico subestimado como droga cardiovascular experimental?

PURPOSE: The rationale of the present review is to analize the activity of Rosmarinus officinalis in the the cardiovascular system METHODS: A MEDLINE database search (from January 1970 to December 2011) using only rosmarinic acid as searched term. RESULTS: The references search revealed 509 references about rosmarinic acid in 40 years (the first reference is from 1970). There is a powerful prevalence of antioxidant and cancer studies. Other diseases are few cited, as inflammation, brain (Alzheimer and Parkinson disease) and, memory; allergy; diabetes; atherosclerosis, and; hypertension. It is necessary to consider the complete absence of studies on coronary artery disease, myocardial ischemia, heart failure or ischemia/reperfusion injury. CONCLUSION: Rosmarinic acid is underestimated as an experimental cardiovascular drug and deserves more attention.

OBJETIVO: A justificativa da revisão é analisar a atividade de Rosmarinus officinalis no sistema cardiovascular MÉTODOS: Uma busca de banco de dados MEDLINE (de janeiro de 1970 a dezembro de 2011), utilizando apenas o ácido rosmarínico como termo pesquisado. RESULTADOS: A busca referências revelou 509 referências sobre o ácido rosmarínico em 40 anos (a primeira referência é de 1970). Há uma prevalência poderoso antioxidante e estudos do câncer. Outras doenças são citados alguns, como o cérebro, inflamação (de Alzheimer e doença de Parkinson) e, a memória, hipertensão, alergia, diabetes, aterosclerose, e. É necessário ter em conta a ausência completa de estudos sobre a doença de artéria coronária, isquemia do miocárdio, insuficiência cardíaca ou isquemia / lesão de reperfusão. CONCLUSÃO: O ácido rosmarínico é subestimado como uma droga experimental cardiovascular e merece mais atenção.