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Vasoactive Intestinal Protein (VIP) is a 28 amino acid neuropeptide that has several effects in several systems. These include the cardiovascular system, respiratory systerm, urinary system, immune system, etc. Furthermore, some of the effects appear to clash with each other. For example, studies have shown that VIP can have an antidipsogenic effect, while some have shown that it induces the secretion of vasopressin. Vasopressin is usually secreted when there is not enough water in the body. Thus, it seems contradictory that the hormone would induce cessation of thirst and secretion of vasopressin.

The hormone is a paracrine mediator. This makes sense since limiting the distance that VIP travels allows for the hormone to only reach the intended tissues. However, it is also a neurohormone. Which means that it travels through blood and I would assume that it causes a myriad of effects. My question is, how does the body make sure that VIP does what is intended to do?

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Vasoactive intestinal peptide (VIP) acts in the intestine, brain, kidneys, lungs, heart, blood vessels, etc. (Cardiovasc Res) and its effects all lead to the same goal: to improve the delivery of blood, glucose and oxygen to the tissues, so it's not a problem if it acts on different tissues simultaneously. Specifically, VIP stimulates thirst, water retention and blood flow through the coronary and pulmonary arteries, dilates bronchi and breaks down glycogen to glucose, among other.

VIP can act via the nerves as a neurotransmitter or via the blood as a hormone:

In research animals and in humans, VIP, administered into the coronary artery or intravenously, increases the epicardial coronary artery cross-sectional area, decreases coronary vascular resistance, and significantly increases coronary artery blood flow. High frequency parasympathetic (vagal) nerve stimulation also releases endogenous VIP in the coronary vessels and heart and significantly increases coronary artery blood flow. (Cardiovasc Res)

In humans, VIP stimulates water retention and thirst:

1) VIP stimulates the secretion of renin:

VIP has now been shown to produce an increase in renin release in a number of species, including humans. (Ann N Y Acad Sci)

The activation of renin-angiotensin-aldosteron system results in water retention.

2) VIP stimulates the secretion of vasopressin (Cardiovascular Research). Vasopressin stimulates water retention. Since vasopressin (arginin-vasopressin or AVP) is dipsogenic (stimulating thirst):

given the established dipsogenic effect of AVP in the nonpregnant state... (JCI Insight)

and since VIP stimulates the secretion of vasopressin, VIP is also dipsogenic.

Now, there seems to be some conflict in the studies about VIP being dipsogenic or anti-dipsogenic in rats:

VIP was found to have no effect on drinking when injected centrally and peripherally in the eel, although it is dipsogenic in the rat after central injection. (ResearchGate)

Intracerebroventricular administration of vasoactive intestinal peptide strongly inhibited drinking in rats deprived of water... (Neuropharmacology)

Not to go in the details, but there may be different circumstances, for example, the level of dehydration, in which VIP can act differently...

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