Vasoactive Intestinal Peptide (VIP): Biology, VIPoma, and Aviptadil

Vasoactive intestinal peptide (VIP) is a small but versatile signaling molecule found throughout the body. First identified in the gut, it turned out to be widely distributed in nerves of the intestine, lungs, blood vessels, and brain. Its name captures two of its core actions — it is vasoactive (it relaxes blood vessels) and it was first isolated from the intestine — but its influence extends much further.

What VIP is and does

VIP is a peptide hormone and neurotransmitter belonging to the same family as secretin and glucagon. Rather than circulating as a classic bloodborne hormone, it acts largely as a local signal released from nerve endings. Its principal effects include:

• Smooth-muscle relaxation — VIP relaxes vascular smooth muscle, causing vasodilation, and relaxes smooth muscle in the gut and airways.
• Secretion — in the intestine it stimulates the secretion of water and electrolytes into the lumen.
• Bronchodilation and pulmonary effects — VIP is abundant in the lung, where it relaxes airways and influences blood flow, a property central to its therapeutic interest.
• Immune and neural modulation — VIP has anti-inflammatory and neuroprotective roles that remain areas of active study.

These actions make VIP a broad "relax and secrete" signal, complementing the many other gut peptides that shape digestion and physiology.

When there is too much: VIPoma

The clearest illustration of what VIP does comes from a rare tumor that overproduces it. A VIPoma is an uncommon neuroendocrine tumor, usually of the pancreas, that secretes large amounts of VIP into the blood. The excess drives VIP's secretory action to an extreme, causing profuse watery diarrhea with loss of potassium and dehydration — a picture historically called WDHA syndrome (watery diarrhea, hypokalemia, achlorhydria). It demonstrates vividly that VIP's job is to push fluid into the gut and relax its muscle.

Treatment of VIPoma centers on controlling the hormone excess and the tumor itself. Somatostatin analogs such as octreotide and lanreotide suppress VIP secretion and are a mainstay of symptom control, alongside fluid and electrolyte replacement and, where feasible, surgery. This mirrors how somatostatin analogs are used to blunt hormone excess in other neuroendocrine syndromes.

VIP as a drug: aviptadil

Because VIP relaxes airways and pulmonary blood vessels and has anti-inflammatory properties, researchers have asked whether giving it as a medicine could help diseased lungs. Aviptadil is a synthetic form of VIP developed for this purpose.

Its most studied application is in acute respiratory distress syndrome (ARDS), including ARDS caused by COVID-19, where it has been investigated as a way to protect and support the injured lung. The evidence from trials has been mixed, and aviptadil is not an approved treatment for ARDS; it remains investigational. See aviptadil for ARDS for a fuller discussion.

A separate, long-established use exists in men's health: combined with phentolamine (a formulation known as Invicorp), VIP is approved in some European countries, including the UK, for erectile dysfunction by intracavernosal injection, exploiting the very same vasodilatory action.

The bigger picture

VIP is a good example of how one molecule's single core property — relaxing smooth muscle and promoting secretion — can appear as a disease when overproduced (VIPoma), as a treatment target when suppressed (somatostatin analogs), and as an investigational drug when its actions might help a struggling organ (aviptadil in ARDS). Understanding its biology ties together gastroenterology, endocrinology, and critical-care research.

> This article is educational and not medical advice. VIP-related medicines, including aviptadil, are prescription or investigational and are used only under clinical supervision.