Biphasic augmentation of alpha-adrenergic contraction by plumbagin in rat systemic arteries.
10.4196/kjpp.2017.21.6.687
- Author:
Hae Jin KIM
1
;
Hae Young YOO
;
Yin Hua ZHANG
;
Woo Kyung KIM
;
Sung Joon KIM
Author Information
1. Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea. sjoonkim@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Artery;
Contraction;
Plumbagin;
Protein kinase C;
Smooth muscle
- MeSH:
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt;
Animals;
Arteries*;
Catalase;
Coronary Vessels;
Femoral Artery;
Mesenteric Arteries;
Muscle, Smooth;
NADPH Oxidase;
Phenylephrine;
Plants;
Protein Kinase C;
Rats*;
Relaxation;
Renal Artery;
Vasoconstrictor Agents
- From:The Korean Journal of Physiology and Pharmacology
2017;21(6):687-694
- CountryRepublic of Korea
- Language:English
-
Abstract:
Plumbagin, a hydroxy 1,4-naphthoquinone compound from plant metabolites, exhibits anticancer, antibacterial, and antifungal activities via modulating various signaling molecules. However, its effects on vascular functions are rarely studied except in pulmonary and coronary arteries where NADPH oxidase (NOX) inhibition was suggested as a mechanism. Here we investigate the effects of plumbagin on the contractility of skeletal artery (deep femoral artery, DFA), mesenteric artery (MA) and renal artery (RA) in rats. Although plumbagin alone had no effect on the isometric tone of DFA, 1 µM phenylephrine (PhE)-induced partial contraction was largely augmented by plumbagin (ΔT(Plum), 125% of 80 mM KCl-induced contraction at 1 µM). With relatively higher concentrations (>5 µM), plumbagin induced a transient contraction followed by tonic relaxation of DFA. Similar biphasic augmentation of the PhE-induced contraction was observed in MA and RA. VAS2870 and GKT137831, specific NOX4 inhibitors, neither mimicked nor inhibited ΔT(Plum) in DFA. Also, pretreatment with tiron or catalase did not affect ΔT(Plum) of DFA. Under the inhibition of PhE-contraction with L-type Ca²⁺ channel blocker (nifedipine, 1 µM), plumbagin still induced tonic contraction, suggesting Ca²⁺-sensitization mechanism of smooth muscle. Although ΔT(Plum) was consistently observed under pretreatment with Rho A-kinase inhibitor (Y27632, 1 µM), a PKC inhibitor (GF 109203X, 10 µM) largely suppressed ΔT(Plum). Taken together, it is suggested that plumbagin facilitates the PKC activation in the presence of vasoactive agonists in skeletal arteries. The biphasic contractile effects on the systemic arteries should be considered in the pharmacological studies of plumbagin and 1,4-naphthoquinones.
