NDLI: Pimaradienoic acid inhibits vascular contraction and induces hypotension in normotensive rats

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Pimaradienoic acid inhibits vascular contraction and induces hypotension in normotensive rats

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Pimaradienoic acid inhibits vascular contraction and induces hypotension in normotensive rats

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Tirapelli, Carlos R. Dos Anjos Neto Filho, Mario Bonaventura, Daniella Melo, Mirian C. C. Ambrosio, Sergio R. de Oliveira, Ana M. Bendhack, Lusiane M. da Costa, Fernando B.
Description	Country affiliation: Brazil Author Affiliation: Tirapelli CR ( Department of Psychiatry Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, University de São Paulo, Ribeirão Preto, SP, Brazil. crtirapelli@eerp.usp.br)
Abstract	The present investigation was designed to investigate the effect of the diterpene ent-pimara-8(14),15-dien-19-oic acid (pimaradienoic acid, PA) on smooth muscle extracellular $Ca^{2+}$ influx. To this end, the effect of PA on phenylephrine- and KCl-induced increases in cytosolic calcium concentration $([Ca^{2+}]_{c}),$ measured by the variation in the ratio of fluorescence intensities (R340/380 nm) of Fura-2, was analysed. Whether bolus injection of PA could induce hypotensive responses in conscious normotensive rats was also evaluated. PA inhibited the contraction induced by phenylephrine (0.03 or 10 μmol $L^{−1})$ and KCl (30 or 90 μmol $L^{−1})$ in endothelium-denuded rat aortic rings in a concentration dependent manner. Pre-treatment with PA (10, 100, 200 μmol $L^{−1})$ attenuated the contraction induced by $CaCl_{2}$ (0.5 nmol $L^{−1}$ or 2.5 μmol $L^{−1})$ in denuded rat aorta exposed to $Ca^{2+}-free$ medium containing phenylephrine (0.1 μmol $L^{−1})$ or KCl (30 μmol $L^{−1}).$ Interestingly, the inhibitory effect displayed by PA on $CaCl_{2}-induced$ contraction was more pronounced when KCl was used as the stimulant. Phenylephrine- and KCl-induced increases in $[Ca^{2+}]_{c}$ were inhibited by PA. Similarly, verapamil, a $Ca^{2+}-channel$ blocker, also inhibited the increase in $[Ca^{2+}]_{c}$ induced by either phenylephrine or KCl. Finally, bolus injection of PA (1–15 mg $kg^{−1})$ produced a dose-dependent decrease in mean arterial pressure in conscious normotensive rats. The results provide the first direct evidence that PA reduces vascular contractility by reducing extracellular $Ca^{2+}$ influx through smooth muscle cellular membrane, a mechanism that could mediate the hypotensive response induced by this diterpene in normotensive rats.
File Format	HTM / HTML
ISSN	00223573
Issue Number	4
Volume Number	60
e-ISSN	20427158
Journal	Journal of Pharmacy and Pharmacology
Language	English
Publisher	Wiley
Publisher Date	2008-04-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Blood Pressure Drug Effects Diterpenes Pharmacology Muscle, Smooth, Vascular Vasodilator Agents Animals Aorta, Thoracic Physiology Calcium Metabolism Calcium Chloride Cytosol Administration & Dosage Dose-response Relationship, Drug In Vitro Techniques Injections, Intravenous Male Muscle Contraction Phenylephrine Rats Rats, Wistar Vasoconstriction Vasoconstrictor Agents Verapamil Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmaceutical Science

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