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.

In healthy human volunteers, compare venous constriction response to endothelin-1 infusion before and after intravenous infusion of glyceryl trinitrate versus saline placebo, measuring maximal venoconstriction via venous plethysmography; duration: single-session, 2–4 hours.

Using surgically harvested human subcutaneous veins, measure tension changes in response to endothelin-1 with and without pre-treatment with glyceryl trinitrate, quantifying reduction in maximal contractile force; duration: acute, 30–60 minutes.

Compare venoconstriction response to endothelin-1 in patients receiving chronic glyceryl trinitrate therapy versus matched controls not receiving it, measuring maximal constriction under controlled infusion conditions.

In transgenic mice expressing human endothelin-A receptors in venous smooth muscle, test whether glyceryl trinitrate reduces endothelin-1-induced venous constriction, mimicking human physiology.

Correlate plasma nitric oxide metabolites with degree of venoconstriction during endothelin-1 challenge in humans, with and without glyceryl trinitrate administration.