MIRABEGRON INDUCED RELAXATION OF ISOLATED BOVINE CORONARY SEGMENTS: ROLE OF NO AND K+ CHANNEL

Georgian Med News. 2024 Feb:(347):87-92.

Abstract

It was already known that mirabegron, a β3-adrenoceptor agonist, affected cardiac muscle, data also demonstrated that mirabegron induced a relaxant effect in rat aortic vessels by a mechanism dependent on nitric oxide production. This study examined the possible effects of mirabegron on the coronary vascular tone. Results show that mirabegron induced an acute relaxant effect on coronary segments' contractility, and the relaxation is partly dependent on nitric oxide and K+ channel activation. These findings emphasize the need to consider these mechanisms when translating mirabegron's effects to clinical applications. Mirabegron, the first approved β3-adrenoceptor agonist, has demonstrated positive effects in heart failure. Research indicates that β3 agonists induce prompt relaxation in rat aortic and human coronary vessels through a pathway mediated by NO. This study examined mirabegron's influence on bovine coronary segments' contractility. Using isolated tissue baths, the impact of mirabegron on bovine coronary artery segments' contractility was assessed. The plasma level of NO was measured with a specialized kit. NO was determined by measuring plasma nitrite concentrations by spectrophotometric analysis at 540 nm. Mirabegron evoked relaxation in bovine coronary artery segments in a dose-dependent manner. However, this effect was inhibited by the presence of potassium chloride (KCl) (70mM) and methylene blue (30μM). Both potassium channel and NO pathways were found to play a role in the relaxations induced by mirabegron. Furthermore, mirabegron was observed to enhance in vivo nitric oxide (NO) levels, a crucial signaling molecule maintaining cardiovascular equilibrium. Our findings illustrate that mirabegron induces coronary vessel relaxation through the activation of both NO and K+ channels. These findings emphasize the need to consider these mechanisms when translating mirabegron's effects to clinical applications.

MeSH terms

  • Acetanilides*
  • Animals
  • Cattle
  • Coronary Vessels
  • Heart*
  • Humans
  • Nitric Oxide*
  • Rats
  • Receptors, Adrenergic
  • Thiazoles*

Substances

  • mirabegron
  • Nitric Oxide
  • Receptors, Adrenergic
  • Acetanilides
  • Thiazoles