Premium
Inhibition of paracrine angiotensin‐converting enzyme in vivo : effects on interstitial glucose and lactate concentrations in human skeletal muscle
Author(s) -
MÜLLER M.,
FASCHING P.,
SCHMID R.,
BURGDORFF T.,
WALDHÄUSL W.,
EICHLER H. G.
Publication year - 1997
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1997.1920746.x
Subject(s) - microdialysis , medicine , endocrinology , basal (medicine) , skeletal muscle , chemistry , interstitial fluid , paracrine signalling , glucose uptake , renin–angiotensin system , insulin , receptor , dopamine , blood pressure
Microdialysis was used to selectively assess the effect of the paracrine renin–angiotensin system (RAS) on interstitial glucose and lactate concentration profiles in skeletal muscle of healthy volunteers ( n = 8) during basal and insulin‐stimulated conditions. Paracrine RAS was selectively inhibited by local retrodialysis with enalaprilate. Under basal conditions, local administration of enalaprilate (2 μg mL −1 ) increased interstitial dialysate glucose concentration from 0.71 ± 0.14 mmol L −1 to 0.84 ± 0.14 mmol L −1 and decreased the serum interstitial gradient (SIG glu ) compared with baseline ( P < 0.02). Under clamp conditions, enalaprilate, even at the lowest concentration (0.02 μg mL −1 ), increased interstitial dialysate glucose concentration from 0.77 ± 0.11 mmol L −1 to 1.02 ± 0.09 mmol L −1 and decreased SIG glu compared with baseline ( P < 0.01). Interstitial lactate concentrations slightly increased during basal as well as during clamp conditions ( P < 0.05 vs. baseline). Selective inhibition of paracrine muscle angiotensin‐converting enzyme (ACE) increases interstitial glucose and lactate concentrations and decreases SIG glu in muscle by facilitating transcapillary glucose transport. This effect is more pronounced during hyperinsulinaemia and may be of clinical relevance in diabetic patients treated with therapeutic doses of enalapril.