Dexmedetomidine-induced contraction of isolated rat aorta is dependent on extracellular calcium concentration.
10.4097/kjae.2012.63.3.253
- Author:
Seong Ho OK
1
;
Sung Il BAE
;
Haeng Seon SHIM
;
Ju Tae SOHN
Author Information
1. Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Jinju, Korea. jtsohn@nongae.gsnu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Aorta;
Calcium;
Contraction;
Dexmedetomidine;
Voltage-operated calcium channel
- MeSH:
Administration, Intravenous;
Analgesia;
Animals;
Aorta;
Calcium;
Calcium Channels;
Contracts;
Dexmedetomidine;
Estrenes;
Gadolinium;
Hypertension;
Inositol 1,4,5-Trisphosphate;
Isotonic Solutions;
Muscle, Smooth;
Muscle, Smooth, Vascular;
Perioperative Period;
Pyrrolidinones;
Rats;
Sarcoplasmic Reticulum;
Type C Phospholipases;
Vasoconstriction;
Verapamil;
Yohimbine
- From:Korean Journal of Anesthesiology
2012;63(3):253-259
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist that is widely used for sedation and analgesia during the perioperative period. Intravenous administration of dexmedetomidine induces transient hypertension due to vasoconstriction via the activation of the alpha2-adrenoceptor on vascular smooth muscle. The goal of this in vitro study is to investigate the calcium-dependent mechanism underlying dexmedetomidine-induced contraction of isolated endothelium-denuded rat aorta. METHODS: Isolated endothelium-denuded rat thoracic aortic rings were suspended for isometric tension recording. Cumulative dexmedetomidine concentration-response curves were generated in the presence or absence of the following inhibitors: alpha2-adrenoceptor inhibitor rauwolscine; voltage-operated calcium channel blocker verapamil (5 x 10(-7), 10(-6) and 5 x 10(-5) M); purported inositol 1,4,5-trisphosphate receptor blocker 2-aminoethoxydiphenylborate (5 x 10(-6), 10(-5) and 5 x 10(-5) M); phospholipase C inhibitor U-73122 (10(-6) and 3 x 10(-6) M); and store-operated calcium channel inhibitor gadolinium chloride hexahydrate (Gd3+; 5 x 10(-6) M). Dexmedetomidine concentration-response curves were also generated in low calcium concentrations (1 mM) and calcium-free Krebs solution. RESULTS: Rauwolscine, verapamil, and 2-aminoethoxydiphenylborate attenuated dexmedetomidine-induced contraction in a concentration-dependent manner. Low calcium concentrations attenuated dexmedetomidine-induced contraction, and calcium-free Krebs solution nearly abolished dexmedetomidine-induced contraction. However, U-73122 and Gd3+ had no effect on dexmedetomidine-induced contraction. CONCLUSIONS: Taken together, these results suggest that dexmedetomidine-induced contraction is primarily dependent on extracellular calcium concentrations that contribute to calcium influx via voltage-operated calcium channels of isolated rat aortic smooth muscle. Dexmedetomidine-induced contraction is mediated by alpha2-adrenoceptor stimulation. Dexmedetomidine-induced contraction appears to be partially mediated by calcium release from the sarcoplasmic reticulum.
