5th February 2024

Regulation of vascular tone

Vascular tone is controlled by several factors, including local and extrinsic factors (adrenaline, noradrenaline, acetylcholine, etc.). We will be focusing on the local factors in this section. Agents in this group act as paracrine signalling agents to allow communication with adjacent cells. The vascular endothelium plays a vital role in controlling the vascular tone.

We will focus on the two most essential agents: nitric oxide and endothelin-1.

Nitric oxide

Nitric oxide is a potent vasodilator and is produced by nitric oxide synthase. This is produced from L-arginine and NADPH acting as electron donors. This eventually produces citrulline and nitric oxide. It has a relatively short half-life and acts locally to increase cellular concentrations of cGMP, activating other cellular processes.

Nitric oxide is also produced in other cells, including platelets, macrophages, neutrophils, hepatocytes and smooth muscle cells.

The function of nitric oxide includes:

• Microvascular tone control in organs
• Inhibition of platelet aggregation
• Vasodilation of the systemic circulation
• Neurotransmission
• Immune response is predominantly by phagocytes

Disorders resulting in imbalances in the production or generation of nitric oxide include hepatorenal syndrome, pulmonary hypertension, and CNS cell death.

Medication like nitro-glycerine is directly converted into nitric oxide by the body. Sildenafil acts to increase the levels of cGMP, which nitric oxide is responsible for producing through its action on guanylate cyclase.

Endothelin-1

Endothelin-1 is produced in response to vascular stresses, including shear forces, hypoxia and increased plasma volumes. Endothelin receptors induce vasoconstriction in most systemic circulation but result in vasodilation in the capillary beds.

Reference

• Maitra, A., Kumar, V., Abbas, A. K., & Aster, J. C. (2013). Inflammation and Repair. In Robbin’s Basic Pathology (9th ed.): Elsevier.
• Chapter 7. Vascular control. Mohrman D.E., & Heller L(Eds.), (2014). Cardiovascular Physiology, 8e. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=843&sectionid=48779655