INCREASED TISSUE NEUTRAL ENDOPEPTIDASE-24.11 ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE HAMSTERS

The purpose of this study was to determine whether tissue neutral endo peptidase (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 hams ters relative to genetically/age-matched normotensive hamsters. Mean a rterial pressure and heart rate were 163 +/- 11 mm Hg and 312 +/- 7 be ats/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, che ek pouch, and spinotrapezius muscle, and significantly decreased in th e heart and aorta of spontaneously hypertensive hamsters relative to c ontrols (P < .05). Lung and brain NEP 24.11 activity is similar in bot h groups. Renal NEP 24.11 activity increases and to a similar extent i n spontaneously hypertensive and normotensive hamsters as chloride ani on concentration in the assay buffer is increased. Substituting citrat e for chloride anion significantly attenuates renal NEP 24.11 activity . Taken together, these data indicate that NEP 24.11 activity in spont aneously hypertensive hamsters is increased in two organs that contrib ute appreciably to peripheral vascular resistance, skeletal muscle, an d kidney. We suggest that the spontaneously hypertensive hamster is a suitable model to study the role of skeletal muscle and renal NEP 24.1 1 in regulating vasomotor tone in essential hypertension. (C) 1998 Ame rican Journal of Hypertension, Ltd.