Cyclic Guanosine Monophosphate (cGMP)

What Is cGMP?

Cyclic Guanosine Monophosphate (cGMP)  is a form of guanosine monophosphate (GMP). Guanosine Monophosphate is in the form of a nucleotide that is composed of guanine, ribose and a phosphate group. cGMP is a cyclic structure, particularly esterified to a sugar moiety in both 3′-and 5′ positions.

It is a second-messenger molecule synthesized by guanylyl cyclases, that plays a key role in cellular signaling pathways by regulating cyclic nucleotide levels through interactions with phosphodiesterases.

How Does cGMP Work?

Cyclic Guanosine Monophosphate is an enzyme that helps in relaxing and widening the blood vessel muscle to allow proper blood flow.  In connection with erectile dysfunction, an enzyme called PDE5 (phosphodiesterase-type5) breaks down cGMP due to the fact that proper blood flow into the penis is obstructed.

It is the role of PDE5 inhibitors to reduce the action of PDE5 enzymes. Once the action of PDE5 is inhibited or reduced by the PDE5 inhibitors, cGMP facilitates blood flow into the penis that results in better and stiffer erections.

As cGMP plays a crucial role in the relaxation and proliferation of smooth muscles. If the system gets interrupted, high blood pressure, angina pectoris, thromboses and other cardiovascular symptoms might arise.

What Is The Function Of Phosphodiesterase Type 5 (PDE5)?

Phosphodiesterase type 5 inhibitors, or PDE5 inhibitors, are a class of medications that treats erectile dysfunction or impotence in men by improving blood flow to the penis. In connection to cGMP, PDE5 inhibitors block the action of PDE5 enzyme that helps cGMP facilitate increased blood flow into the penis, which results in better and stiffer erections.

Clinical Relevance:

Inhibitors of PDE5 or drugs such as sildenafil, tadalafil and vardenafil are used to treat erectile dysfunction by maintaining an erection in response to sexual stimulation.

In summary, PDE5 regulates the action of cGMP by breaking it down, thus controlling smooth muscle tone and blood vessel dilation in various tissues.

What Are The Health Conditions That Interfere With cGMP?

Cyclic Guanosine Monophosphate is involved in various physiological processes that includes vasodilation, platelet function, vision and the regulation of smooth muscle relaxation. cGMP sends signals to widen the blood vessels. Any disruption in the signaling can contribute to a range of health conditions. The key health conditions that interfere with or are influenced by cGMP signaling are:

Cardiovascular diseases:

Hypertension or high blood pressure: abnormalities in cGMP signaling can lead to impaired vasodilation that contributes to the development of high blood pressure.

Heart Failure:

The reduction in cGMP levels can impair the function of cardiac cells. It leads to diminished heart contractility and relaxation and can contribute to heart failure.

Atherosclerosis: The breakage in cGMP signaling may interfere with endothelial function and contribute to the development of atherosclerosis. It is a condition characterized by the hardening and narrowing of arteries.

Neurological disorders:

Alzeiher’s disease: cGMP also involves synaptic plasticity and memory formation.  Impaired cGMP signaling has been implicated in cognitive decline that is observed in Alzheimer’s disease.

Parkinson’s disease:

The interference in cGMP signaling might affect the dopaminergic pathways, contributing to the movement disorders that is seen in Parkinson’s disease.

Migraine:

The vasodilation effects of cGMP that take place in cerebral blood vessels are believed to be involved in the onset of migraines. The disruptions in cGMP can trigger the migraine attacks.

Kidney disorders:

In chronic kidney disease, the renal vasculature and glomerular function can be impaired partly due to the alteration in cGMP signaling. This condition can contribute to worsening the kidney functions.

Nephropathy:

cGMP involves regulating the blood flow to the kidneys. The disturbances in the signaling leads to conditions like diabetic nephropathy or hypertension-related kidney damage.

Pulmonary diseases:

It is a condition that causes reduction in cGMP levels. This contributes to constricted pulmonary arteries that result in high blood pressure in the lungs. It can lead to heart failure over time.

Chronic Obstructive Pulmonary Disease (COPD):

The abnormal irregularities in the airways can contribute to the airway remodelling and cause vascular dysfunction in COPD.

Diabetes and Metabolic disorders:

The alteration in cGMP signaling contributes to the vascular changes and retinal damage that is associated with diabetic retinopathy ( a common complication caused due to diabetes).

Insulin resistance: There are certain in-vitro studies that suggest that disrupted cGMP signaling might impair insulin action that might lead to insulin resistance.

Cancer:

Tumour growth: The cancer cells manipulate and interfere signaling pathways that promote survival, new blood vessel formation and metastasis. The dysregulation of cGMP is associated with various cancers that include breast, lung and prostate.

Colorectal cancer: The signaling of cGMP has been shown to play a role in regulating cell growth and programmed cell death, with some cancer cells bypassing normal cGMP-mediated regulation.

Retinal And Vision Disorders:

cGMP plays a vital role in the phototransduction pathway in the retina. The disturbances that are caused in the mutations of enzymes that regulate cGMP levels can cause loss of vision. This is observed in conditions like retinitis pigmentosa.

Infectious diseases:

Malaria: Plasmodium is a parasite that causes malaria and manipulates host cGMP pathways to promote its survival within the red blood cells.

Hormonal Imbalances:

Endocrine disorders: The hormones such as atrial natriuretic peptide (BNP). This regulates cGMP production that involves fluid balance, blood pressure and heart function. The dysfunction in cGMP signaling can be found in disorders of the thyroid, pituitary and adrenal glands.