Direct angiotensin converting enzyme inhibitor-mediated venodilation.
BACKGROUND
The vasodilator effects of angiotensin converting enzyme inhibitors have been ascribed to systemic inhibition of the angiotensin II generation. However, local mechanisms of vasodilation also have been suggested. We tested whether the angiotensin converting enzyme inhibitor enalaprilat mediated local vasodilation in human dorsal hand veins.


METHODS
We infused enalaprilat and assessed changes in dorsal hand vein compliance using the linear variable differential transducer technique. Enalaprilat-mediated effects were assessed in small and large veins and in the presence and absence of one of two vasoconstrictors: exogenous norepinephrine or physiologic vasoconstriction by cooling.


RESULTS
We infused locally in small dorsal hand veins at skin temperatures of less than 29.0 degrees C (baseline distention < 0.35 mm) in the absence of exogenous vasoconstrictors, enalaprilat mediated dose-dependent vasodilation (median effective dose [ED50], 12 ng/min to a maximal effect of 162% +/- 15% of baseline, p < 0.01). Maximal enalaprilat-mediated vasodilation was comparable to dilation mediated by insulin (175% +/-17% of baseline; p = 0.21) and less than dilation mediated by nitroglycerin (221% +/- 20% of baseline; p = 0.011). At skin temperatures > 31 degrees C, enalaprilat mediated dose-dependent vasodilation in small vessels only when vessels were preconstricted with norepinephrine (ED50 = 5.1 ng/min, maximal enalaprilat-mediated effect of 164% +/- 21% of baseline; p < 0.05).


CONCLUSIONS
These data suggest enalaprilat mediates local vasodilation in dorsal hand veins, with an ED50 comparable to plasma enalaprilat concentrations achieved with oral enalapril therapy. This effect is dependent on vessel size and on the presence of preconstruction. Local vasodilator effects may be important in the clinical hemodynamic effects of angiotensin converting enzyme inhibitors.
Zarnke
K B
KB
Department of Medicine, University of Western Ontario, London, Canada.
Feldman
R D
RD
D000328:Adult; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015773:Enalaprilat / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006225:Hand / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D013223:Statistics as Topic; D013696:Temperature; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D005996:Nitroglycerin; D015773:Enalaprilat; D009638:Norepinephrine