Regional norepinephrine spillover in response to angiotensin-converting enzyme inhibition in healthy subjects.
OBJECTIVE
Even though most previous studies have shown that central nervous angiotensin II causes sympatho-excitation, there are data suggesting that blockade of the renin-angiotensin system (RAS) could activate the renal sympathetic nerves. The aim of the present study was to investigate overall, cardiac and renal sympathetic nerve activity, before and after intravenous enalaprilat, in healthy normotensive subjects without an activated RAS.


METHODS
Thirty healthy subjects underwent catheterization of the radial artery, right renal and coronary sinus veins with blood sampling at baseline and 30-40 min after 1.25 or 2.5 mg of intravenous enalaprilat, respectively. Regional and overall sympathetic nervous activity was estimated using isotope dilution, calculating spillovers of norepinephrine.


RESULTS
Mean arterial blood pressure decreased by 5% (P < 0.05) after the higher dose and remained unchanged after the lower dose of enalaprilat, whereas renal norepinephrine spillover increased after both doses by 49 and 26% respectively (P < 0.05 for both). Cardiac and total body norepinephrine spillover remained unchanged after both doses of enalaprilat. Pulmonary capillary wedge pressure, which was measured in eight subjects after 2.5 mg enalaprilat, fell by 43% (P < 0.05).


CONCLUSIONS
In the absence of, or after a minor, blood pressure fall, intravenous enalaprilat selectively activates the renal nerves in healthy subjects without an activated RAS. Unloading of the low-pressure baroreceptor system and/or a central nervous effect of enalaprilat may be responsible for this differentiated sympathetic nervous response.
Johansson
Mats
M
Department of Clinical Physiology, Cardiovascular Institute, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden. m.johansson@medfak.gu.se
Rundqvist
Bengt
B
Petersson
Magnus
M
Lambert
Gavin
G
Friberg
Peter
P
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D006328:Cardiac Catheterization; D015773:Enalaprilat / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D011311:Pressoreceptors / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D015773:Enalaprilat; D009638:Norepinephrine