The α-1 Adrenergic Receptor Antagonist Doxazosin Attenuates Liver Fibrosis by Alleviating Sinusoidal Capillarization

Ai-Yuan Xiu1, Qian Ding2, Chang-Peng Zhu3

  • 1Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China.

Advanced Biology
|March 17, 2024
PubMed

Insights

Doxazosin effectively reduces liver fibrosis and sinusoidal capillarization in a mouse model. This study suggests doxazosin as a potential therapeutic for liver diseases by inhibiting liver angiogenesis.

Area of Science:

  • Hepatology
  • Pharmacology
  • Cell Biology

Background:

  • Liver fibrosis and cirrhosis are critical global health issues stemming from chronic liver injury.
  • Current therapeutic options for these conditions remain limited, necessitating novel treatment strategies.

Purpose of the Study:

  • To investigate the therapeutic potential of doxazosin in mitigating liver fibrosis.
  • To elucidate the underlying mechanisms by which doxazosin affects liver fibrosis and angiogenesis.

Main Methods:

  • A mouse model of liver fibrosis was induced using carbon tetrachloride (CCl4) administration.
  • Doxazosin was administered orally to mice, and liver fibrosis was assessed using histological staining (HE, Masson, Sirius Red) and molecular techniques.
  • In vitro studies on human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs) involved cell viability, western blotting, immunofluorescence, and angiogenesis assays.

Main Results:

  • Doxazosin treatment significantly alleviated liver fibrosis and sinusoidal capillarization in CCl4-induced mice.
  • The drug demonstrated an inhibitory effect on angiogenesis in both HUVECs and HHSECs.
  • Doxazosin reduced liver angiogenesis and sinusoidal capillarization.

Conclusions:

  • Doxazosin shows promise in treating liver fibrosis by targeting sinusoidal capillarization and angiogenesis.
  • The findings support doxazosin as a potential therapeutic agent for chronic liver injury.
  • Further research into doxazosin's role in liver disease is warranted.

Related Concept Videos

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
428
Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers01:22

Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers

α-Adrenergic antagonists, known as α-blockers, exert their effects by inhibiting α-adrenoceptors, leading to specific physiological actions. α1-blockers and α2-blockers have distinct pharmacological actions and therapeutic applications.
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally,...
806
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
726
Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers01:17

Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers

Adrenergic antagonists, or sympatholytics, inhibit adrenoceptor activation driven by catecholamines or agonists. Based on their adrenoceptor specificity, adrenergic blockers can be categorized into two primary groups: α-adrenergic blockers (α-blockers) and β-adrenergic blockers (β-blockers). α-blockers interact with α1 and α2 subtypes of α-adrenoceptors.
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline...
874
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
631
Adrenergic Receptors: ɑ Subtype01:31

Adrenergic Receptors: ɑ Subtype

Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
1.5K