Journal of Applied Physiology, Vol 78, Issue 2 562-568, Copyright © 1995 by American Physiological Society
Neutral endopeptidase modulates substance P-induced vasodilation in vivo
X. P. Gao and I. Rubinstein
Department of Medicine, University of Illinois at Chicago, USA.
The purpose of this study was to investigate whether neutral endopeptidase
(NEP; EC 3.4.24.11) modulates substance P-induced vasodilation in the oral
mucosa in vivo. Using intravital microscopy, we measured the diameter of
second-order arterioles (44-70 microns) in the hamster cheek pouch during
suffusion of capsaicin and substance P. We found that capsaicin (0.1 and
10.0 nM) induced significant concentration-dependent vasodilations (13 +/-
4 and 39 +/- 7% increase from baseline, respectively; P < 0.05) that
were significantly potentiated by phosphoramidon (10.0 nM), a selective NEP
inhibitor (35 +/- 15 and 61 +/- 12% increase from baseline, respectively; P
< 0.05). Substance P (0.1 and 10.0 nM) also induced significant
concentration-dependent vasodilations (7 +/- 3 and 25 +/- 8% increase from
baseline, respectively; P < 0.05) that were mediated by the
COOH-terminal of the molecule. Substance P-induced responses were
significantly potentiated by phosphoramidon (34 +/- 9 and 53 +/- 10%
increase from baseline, respectively; P < 0.05) and thiorphan (10.0
microM), a selective NEP inhibitor (44 +/- 11 and 53 +/- 10% increase from
baseline, respectively; P < 0.05). Substance P-(1-9) had no significant
effects on arteriolar diameter. Suffusion of captopril, leupeptin,
Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid
together had no significant effects on substance P-induced vasodilation.
Phosphoramidon did not potentiate nitroglycerin-induced vasodilation. These
data indicate that NEP modulates substance P-induced vasodilation in the
hamster cheek pouch in vivo. We suggest that any decrease in tissue NEP
activity may amplify neurogenic vasodilation in the oral mucosa.
