Cardiovascular Effects Elicited by Milonine, a New 8,14‐Dihydromorphinandienone Alkaloid

Cavalcante, Horacinna M.M.; Ribeiro, Thais Porto; Silva, Darízy F.; Nunes, Xirley Pereira; Barbosa-Filho, José Maria; Diniz, Margareth F. F. Melo; Correia, N. A.; Braga, Valdir A.; Medeiros, Isac A.

doi:10.1111/j.1742-7843.2010.00631.x

Cited by 18 publications

(12 citation statements)

References 40 publications

(43 reference statements)

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“…Contractions of vascular smooth muscle cells induced by KCl (80 mM) rely almost exclusively on Ca 2+ infl ux through activation of voltage-sensitive channels, (Hirata et al, 1998), whereas contractions induced by Phe are mediated by an increase in Ca 2+ infl ux through both receptor-operated channels with findings reported by others Bastos et al, 2010;Cavalcante et al, 2011). However, this result does not rule out the possibility that EEEP interferes with the sarco-endoplasmatic reticulum Ca 2+ -ATPases.…”

Section: Discussioncontrasting

confidence: 55%

Erythroxylum pungens elicits vasorelaxation by reducing intracellular calcium concentration in vascular smooth muscle cells of rats

Oliveira¹,

Sena-Filho²,

Mendes-Júnior³

et al. 2012

Rev. bras. farmacogn.

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Abstract:The cardiovascular effects elicited by the ethanolic extract obtained from the roots of Erythroxylum pungens O.E. Schulz, Erythroxylaceae (EEEP) and the vasorelaxant effect induced by its main tropane alkaloid (pungencine) were investigated. In normotensive rats, administration of EEEP (1, 10, 30 and 60 mg/kg i.v., randomly) produced dose-dependent hypotension (-2±1, -7±0.5 -17.6±1, -24±1 ∆ mmHg, n=5) followed by tachycardia (3±0.5, 7±2, 7.1±1, 10±5 ∆ bpm, n=5). In intact phenylephrine (Phe, 10 μM)-pre-contracted rings, EEEP (0.01-500 μg/mL) induced concentrationdependent vasorelaxation (EC50 13.7±5.5 μg/mL, Maximal Response= 92±2.6%), and this effect was unchanged after the removal of the vascular endothelium (EC50 27.2±4.7 μg/ml, Maximal Response= 88.3±3.3 %). In KCl (80 mM)-pre-contracted-endotheliumdenuded rings, EEEP elicited concentration-dependent relaxation (EC50= 128.2±11.2 μg/mL, Maximal Response 76.8±3.4%). Vasorelaxation has also been achieved with tonic contractions evoked by the L-type Ca 2+ channel agonist Bay K 8644 (EC50 80.2±9.1 μg/mL, Maximal Response 86.3±8.3%). In addition, in a depolarizing medium, EEEP inhibited CaCl 2 (30-500 μg/mL) induced contractions and caused a concentrationdependent rightward shift of the relaxation curves. Lastly, the tropane alkaloid pungencine caused vasorelaxation in mesenteric arteries resembling to the EEEP responses. These results suggests that EEEP induces hypotension and vasorelaxation, at least in part, due to the reduction in [Ca 2+ ]i in vascular smooth muscle cells.

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Section: Discussioncontrasting

confidence: 55%

Erythroxylum pungens elicits vasorelaxation by reducing intracellular calcium concentration in vascular smooth muscle cells of rats

Oliveira¹,

Sena-Filho²,

Mendes-Júnior³

et al. 2012

Rev. bras. farmacogn.

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“…Isometric tension measurement. Lyon normotensive rats were euthanized by cervical dislocation, and the superior mesenteric arteries were cleaned of adherent tissue as described by Cavalcante and colleagues [22]. Briefly, the superior mesenteric artery was removed and cleaned from connective tissue and fat.…”

Section: Methodsmentioning

confidence: 99%

Rotundifolone-Induced Relaxation is Mediated by BKCa Channel Activation and Cav Channel Inactivation

Silva

Araújo

Albuquerque

et al. 2011

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

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Rotundifolone is the major constituent of the essential oil of Mentha x villosa Hudson. In preliminary studies, rotundifolone induced significant hypotensive, bradycardic and vasorelaxant effects in rats. Thus, to gain more insight into the pharmacology of rotundifolone, the aim of this study was to characterize the molecular mechanism of action involved in relaxation produced by rotundifolone. The relaxant effect was investigated in rat superior mesenteric arteries by using isometric tension measurements and whole-cell patch-clamp techniques. Rotundifolone relaxed phenylephrine-induced contractions in a concentration-dependent manner. Pre-treatment with KCl (20 mM), charybdotoxin (10 )7 M) or tetraethylammonium (TEA 10 )3 or 3 · 10 )3 M) significantly attenuated the relaxation effect induced by rotundifolone. Additionally, whole-cell patch-clamp recordings were made in mesenteric smooth muscle cells and showed that rotundifolone significantly increased K + currents, and this effect was abolished by TEA (10 )3 M), suggesting the participation of BK Ca channels. Furthermore, rotundifolone inhibited the vasoconstriction induced by CaCl 2 in depolarizing nominally Ca 2+-free medium and antagonized the contractions elicited by an L-type Ca 2+ channel agonist, S(-)-Bay K 8644 (2 · 10 )7 M), indicating that the vasodilatation involved inhibition of Ca 2+ influx through L-type voltage-dependent calcium channels (Ca v type-L). Additionally, rotundifolone inhibited L-type Ca 2+ currents (I Ca L), affecting the voltage-dependent activation of I Ca L and steady-state inactivation. Our findings suggest that rotundifolone induces vasodilatation through two distinct but complementary mechanisms that clearly depend on the concentration range used. Rotundifolone elicits an increase in the current density of BK Ca channels and causes a shift in the steady-state inactivation relationship for Ca v type-L towards more hyperpolarized membrane potentials.Terpenoids constitute the largest class of plant secondary metabolites and have been used in essential oils for centuries as therapeutically relevant compounds. However, little is known about their mechanism of action [1,2].The monoterpenoids, such as camphor, borneol, citronellol, alpha-terpineol or menthol, compose a group of naturally occurring organic compounds derived from two isoprene units. They are the major components of some essential oils presenting anaesthetic and analgesic activities [3,4] Rotundifolone (C 10 H 14 O 2 ; molecular weight 166) is a naturally occurring monoterpenic ketone of plant origin and an important chemical constituent of the essential oils of many Mentha species (Mentha rotundifolia, M. suaveolens, M. spicata L., M. longifolia and M. x villosa) [19,20]. A previous report from our group showed that rotundifolone induced marked hypotension and bradycardia in non-anaesthetized normotensive rats using an in vivo approach. Those effects were probably due to a decrease in peripheral vascular resistance [21], a hypothesis that was subsequently str...

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“…The tissues commonly used to test the effects of compounds on the NO/cGMP pathway are isolated rat thoracic aorta rings or arteries from the mesenteric artery bed [ 126 , 187 ]. However, other tissues have been used, such as rat basilar artery [ 115 ], rabbit thoracic aorta [ 230 ], porcine coronary artery [ 113 ], canine coronary artery [ 159 ], and bovine ophthalmic artery [ 31 ].…”

Section: Compounds Acting On the No/cgmp Pathwaymentioning

confidence: 99%

Vasodilator Compounds Derived from Plants and Their Mechanisms of Action

et al. 2013

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The present paper reviews vasodilator compounds isolated from plants that were reported in the past 22 years (1990 to 2012) and the different mechanisms of action involved in their vasodilator effects. The search for reports was conducted in a comprehensive manner, intending to encompass those metabolites with a vasodilator effect whose mechanism of action involved both vascular endothelium and arterial smooth muscle. The results obtained from our bibliographic search showed that over half of the isolated compounds have a mechanism of action involving the endothelium. Most of these bioactive metabolites cause vasodilation either by activating the nitric oxide/cGMP pathway or by blocking voltage-dependent calcium channels. Moreover, it was found that many compounds induced vasodilation by more than one mechanism. This review confirms that secondary metabolites, which include a significant group of compounds with extensive chemical diversity, are a valuable source of new pharmaceuticals useful for the treatment and prevention of cardiovascular diseases.

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Cardiovascular Effects Elicited by Milonine, a New 8,14‐Dihydromorphinandienone Alkaloid

Cited by 18 publications

References 40 publications

Erythroxylum pungens elicits vasorelaxation by reducing intracellular calcium concentration in vascular smooth muscle cells of rats

Erythroxylum pungens elicits vasorelaxation by reducing intracellular calcium concentration in vascular smooth muscle cells of rats

Rotundifolone-Induced Relaxation is Mediated by BKCa Channel Activation and Cav Channel Inactivation

Vasodilator Compounds Derived from Plants and Their Mechanisms of Action

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