Increased tissue neutral endopeptidase 24.11 activity in spontaneously hypertensive hamsters.
The purpose of this study was to determine whether tissue neutral endopeptidase (NEP) 24.11 activity, a membrane-bound metalloenzyme widely distributed in the peripheral circulation that cleaves and inactivates vasodilator peptides, is increased in spontaneously hypertensive hamsters relative to genetically/age-matched normotensive hamsters. Mean arterial pressure and heart rate were 163 +/- 11 mm Hg and 312 +/- 7 beats/min in spontaneously hypertensive hamsters and 99 +/- 3 mm Hg and 302 +/- 10 beats/min in normotensive hamsters, respectively (mean +/- SEM). NEP 24.11 activity is significantly increased in the kidney, cheek pouch, and spinotrapezius muscle, and significantly decreased in the heart and aorta of spontaneously hypertensive hamsters relative to controls (P < .05). Lung and brain NEP 24.11 activity is similar in both groups. Renal NEP 24.11 activity increases and to a similar extent in spontaneously hypertensive and normotensive hamsters as chloride anion concentration in the assay buffer is increased. Substituting citrate for chloride anion significantly attenuates renal NEP 24.11 activity. Taken together, these data indicate that NEP 24.11 activity in spontaneously hypertensive hamsters is increased in two organs that contribute appreciably to peripheral vascular resistance, skeletal muscle, and kidney. We suggest that the spontaneously hypertensive hamster is a suitable model to study the role of skeletal muscle and renal NEP 24.11 in regulating vasomotor tone in essential hypertension.
Vishwanatha
J K
JK
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, USA.
Davis
R G
RG
Blumberg
S
S
Gao
X P
XP
Rubinstein
I
I
D000818:Animals; D000838:Anions / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D006224:Cricetinae / Q000235:genetics; D006020:Glycopeptides / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D015260:Neprilysin / Q000378:metabolism*; D009994:Osmolar Concentration; D011480:Protease Inhibitors / Q000494:pharmacology; D015244:Thiorphan / Q000494:pharmacology
D000838:Anions; D002712:Chlorides; D006020:Glycopeptides; D011480:Protease Inhibitors; D015244:Thiorphan; D015260:Neprilysin; C008890:phosphoramidon