Abstract
Thymol and carvacrol are the main compounds found in Lippia mycrophylla essential oil (LM-OE) and have presented some spasmolytic effects. This work was designed to explore a possible vasorelaxant effect of LM-OE and its major monoterpenes constituents on rat pulmonary artery. For that, the organ was in vitro stimulated with phenylephrine (Phe) 3 mM and over the tonic contraction the relaxant effect of LM-OE, carvacrol and thymol was observed in both intact and denuded-endothelium. Moreover, atropine, L-NAME, indomethacin, 2,3-O-isopropylidene adenosine, H-89 and Y-27632 were incubated before the relaxant curve of thymol over Phe-tonic contraction. Furthermore, the effects of thymol on KCl 30 or 80 mM and S-(−)-Bay K8644-induced tonic contractions were evaluated, as well as its inhibitory effect on CaCl2-induced cumulative contractions. LM-OE, carvacrol and thymol presented relaxant effect on pulmonary artery, thymol was the most potent and its relaxant potency in intact-endothelium preparations was reduced by atropine, L-NAME, indomethacin, 2,3-O-isopropylidene adenosine and H-89, despite there was not change on its maximum relaxat effect. Also, the monoterpene relaxed equipotently KCl 30 or 80 mM pre-contracted pulmonary artery, antagonized CaCl2-induced cumulative contractions and relaxed S-(−)-Bay K8644 pre-contracted organ. Ultimately, thymol relaxant potency was not modified by Y-27632. Therefore, thymol acts by endothelium-dependent and independent mechanisms, possibly positively modulating the endothelial cholinergic pathway, prostanoids release and further activation of AC/PKA and also inhibiting Ca2+ influx through CaV.
Highlights
The use of plants for therapeutic purposes is one of the oldest forms of medicinal practice of humanity (Marques; Filgueiras, 2009)
3.1 Effect of Lippia mycrophylla essential oil (LM-OE), carvacrol and thymol on isolated rat pulmonary artery LM-OE (0.01-729 μg/mL, n = 5) completely relaxed the pulmonary artery rings pre-contracted with Phe 3 μM, in both intact and denuded endothelium, to carvacrol (0.01-243 μg/mL, n = 5); Otherwise, thymol (0.01-243 μg/mL, n = 5), that was more potent in intact endothelium pulmonary artery rings (p
Emax values were achieved with 729 μg/mL for LM-OE, 243 μg/mL for carvacrol and 243 μg/mL for thymol in the presence and absence of endothelium, respectively (Figure 1 and 2A-C, Table 1)
Summary
The use of plants for therapeutic purposes is one of the oldest forms of medicinal practice of humanity (Marques; Filgueiras, 2009). Comparing with other vascular beds, the pulmonary circulation presents some particularities, being a system of low resistance and presenting different pattern of mediators and receptors, such as endothelin, endothelial nitric oxide synthase and prostanoids, acting itself as a system of own and differentiated functioning of the systemic circulation (Sommer et al, 2020; Wang et al, 2021). Several pathological processes may result in acute or chronic increases in the afterload in the right ventricle, such as pulmonary arterial hypertension. Right heart failure may occur and sudden hemodynamic instability and death may occur (Greyson, 2010; Huang et al, 1996; Sommer et al, 2020; Zahid et al, 2020). Substances that relax smooth muscle of the pulmonary vascular bed can lead to a decrease in the afterload of the right ventricle and decreased symptoms of diseases, such as pulmonary arterial hypertension (PAH)
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