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7-Hydroxycoumarin Induces Vasorelaxation in Animals with Essential Hypertension: Focus on Potassium Channels and

Rafael L C Jesus1, Isnar L P Silva1, Fênix A Araújo2

  • 1Laboratory of Cardiovascular Physiology and Pharmacology, Federal University of Bahia, Salvador 40110-902, Brazil.

Molecules (Basel, Switzerland)
|November 11, 2022
PubMed

Insights

7-hydroxycoumarin (7-HC) demonstrates significant antihypertensive effects by relaxing blood vessels through potassium channel activation and calcium influx modulation. This natural compound offers a promising avenue for managing hypertension.

Area of Science:

  • Pharmacology
  • Cardiovascular Research
  • Natural Products Chemistry

Background:

  • Cardiovascular diseases (CVD) are a leading global cause of mortality, with hypertension as the primary risk factor.
  • Despite available treatments, effective blood pressure control remains a challenge for many hypertensive patients.
  • Natural products are vital sources for novel drug discovery, including antihypertensive agents.

Purpose of the Study:

  • To investigate the vascular effects of 7-hydroxycoumarin (7-HC), a natural product with potential antihypertensive properties.
  • To elucidate the mechanisms underlying the vasorelaxant effects of 7-HC in an experimental model of essential hypertension.

Main Methods:

  • Isometric tension measurements were performed on superior mesenteric arteries from spontaneously hypertensive rats (SHR).
  • The relaxant effects of varying concentrations of 7-HC (0.001 μM-300 μM) were assessed.
  • The study examined the involvement of ion channels (KATP, BKCa, Kv) and calcium signaling pathways (IP3, ryanodine receptors).

Main Results:

  • 7-HC induced significant vasorelaxation in the mesenteric arteries of hypertensive rats.
  • The relaxant effect was attributed to the activation of K+-channels (KATP, BKCa, Kv) and modulation of Ca2+ influx.
  • 7-HC reduced responsiveness to α1-adrenergic agonists and enhanced responses to muscarinic agonists and nitric oxide (NO) donors.
  • Endothelium-independent vasorelaxant factors were implicated in 7-HC's mechanism.

Conclusions:

  • 7-hydroxycoumarin exhibits potent endothelium-independent vasorelaxant properties in a model of essential hypertension.
  • Its mechanism involves K+-channel activation and modulation of intracellular calcium release and influx.
  • 7-HC demonstrates potential as a therapeutic agent for hypertension by reducing vasoconstriction and improving vascular relaxation.

Keywords:
7-hydroxycoumarinhypertensive ratsisometric recordssuperior mesenteric artery superiorumbelliferonevasorelaxation

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