A natural substance in the body called endothelin-1, given in a tiny amount, causes veins to tighten up slowly and stay that way for a long time—up to two-thirds narrower—showing it’s a powerful and lasting way to control blood vessel size.

When you give your veins a boost of nitric oxide from a medicine like glyceryl trinitrate, it helps relax them and counteracts a tightening chemical called endothelin-1. But your body’s own nitric oxide doesn’t seem to do much to stop that tightening, because blocking its production doesn’t make the veins tighten more.

Your veins have a natural safety system that helps prevent them from squeezing too tight when a powerful tightening chemical is present; if you block this system with aspirin, the veins squeeze much harder—showing that this safety system is really important.

A medicine called glyceryl trinitrate can help relax tightened veins caused by another substance called endothelin-1, cutting the tightness in half — which shows that nitric oxide, even when not made naturally by the body, can still help open up blood vessels.

Prostacyclin works better than a common heart medication called glyceryl trinitrate to relax veins that have been tightened by another substance, making the veins open up more — it reduces tightening to just 12% instead of 33%.