Propofol Relaxes Isolated Rat Aorta through BK Ca Activation

Ann Vasc Surg. 2019 Oct;60:397-406. doi: 10.1016/j.avsg.2019.04.005. Epub 2019 Jun 12.

Abstract

Background: Propofol is an intravenous anesthetic that can be used for the induction and maintenance of anesthesia. In the present study, it was aimed to investigate the mechanism of vasodilator action of propofol in the rat aorta (RA).

Methods: The RA rings were suspended in isolated organ baths and tension was recorded isometrically. First, potassium chloride (KCl) and phenylephrine (PE) were added to organ baths to form precontraction. When the precontractions were stable, propofol (1, 10, and 100 μM) was added cumulatively to the baths. The antagonistic effect of propofol on KCl (45 mM), PE (1 μM), 5-hydroxytryptamine (5-HT) (30 μM), and calcium chloride (CaCl2) (10 μM to 10 mM) induced contractions in the vascular rings were investigated. Propofol-induced relaxations were also tested in the presence of the K+ channel inhibitors tetraethylammonium (TEA, 1 mM), glibenclamide (GLI, 10 μM), 4-aminopyridine (4-AP, 1 mM), and barium chloride (BaCl2, 30 μM).

Results: Preincubation with propofol (1, 10, and 100 μM) did not affect the basal tone but inhibited the contraction induced by KCl, PE, 5-HT, and CaCl2-induced contractions. Propofol-induced relaxation was not effected by 4-AP, GLI, and BaCl2. However, TEA inhibited propofol-induced relaxations significantly.

Conclusions: The propofol induces relaxation in contracted RA and inhibits KCl, PE, 5-HT, and CaCl2-induced contractions. The results demonstrate that the mechanism of action of propofol-induced vasodilation in the RA may be related to large conductance Ca2+-activated K+ channel activation.

MeSH terms

  • Animals
  • Aorta / drug effects*
  • Aorta / metabolism
  • Female
  • In Vitro Techniques
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / agonists*
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / metabolism
  • Propofol / pharmacology*
  • Rats, Wistar
  • Signal Transduction
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology*

Substances

  • Kcnma1 protein, rat
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Vasodilator Agents
  • Propofol