Direct angiotensin converting enzyme inhibitor-mediated venodilation

Area of Science:

• Pharmacology
• Cardiovascular Physiology

Background:

• Angiotensin converting enzyme inhibitors (ACEIs) are known for systemic vasodilation via angiotensin II inhibition.
• Local mechanisms of vasodilation by ACEIs have been proposed but not fully elucidated.
• This study investigated the local vasodilator effects of enalaprilat in human dorsal hand veins.

Purpose of the Study:

• To determine if the ACE inhibitor enalaprilat induces local vasodilation in human dorsal hand veins.
• To assess the dose-dependency and conditions influencing enalaprilat-mediated vasodilation.
• To compare the local vasodilator potency of enalaprilat with other agents.

Main Methods:

• Infusion of enalaprilat into human dorsal hand veins.
• Measurement of vein compliance using the linear variable differential transducer technique.
• Assessment of effects in small and large veins, with and without exogenous norepinephrine or cooling-induced vasoconstriction.

Main Results:

• Enalaprilat induced dose-dependent vasodilation in small dorsal hand veins at cooler temperatures (ED50 = 12 ng/min).
• Maximal vasodilation with enalaprilat was comparable to insulin and less than nitroglycerin.
• In warmer conditions, enalaprilat required norepinephrine preconstriction for vasodilation in small vessels (ED50 = 5.1 ng/min).

Conclusions:

• Enalaprilat mediates local vasodilation in dorsal hand veins.
• The local vasodilator effect is dependent on vessel size and the presence of vasoconstriction.
• These local effects may play a role in the clinical hemodynamic actions of ACE inhibitors.