Acute neutral endopeptidase inhibition is natriuretic in old rats.

Abstract:

:Neutral endopeptidase 24.11 (NEP) inhibitors prevent breakdown of atrial natriuretic peptide (ANP), and may be useful therapeutically, in sodium overload states as often occurs in the aged. However, age-dependent changes in ANP/NEP may limit the activity of these agents in the elderly. To investigate this we conducted experiments in young, middle aged and old conscious male rats, studied in the baseline euvolemic state and during acute NEP inhibition (NEPI). NEPI produced a marked increase in sodium excretion (>100%) in all groups, regardless of age. A selective, potassium sparing effect was also seen, only in the middle-aged and old rats. Although baseline hemodynamics were affected by age with mean blood pressure, BP, and renal vascular resistance (RVR) being higher in old versus young (131+/-5 vs. 115+/-3 mmHg; P<0.05 and 29+/-3 vs. 20+/-1 mmHg/ml per min per 100 g body weight (BW); P<0.02, respectively); NEPI produced similar mild pressor and significant renal vasoconstrictor effects in all age groups. Despite the tendency of NEPI to reduce renal perfusion, this is an effective method of increasing sodium excretion in all age groups while the potassium sparing actions seen selectively in the older rats may increase the usefulness of NEPI as a diuretic agent for the elderly.

journal_name

Mech Ageing Dev

authors

Greenfeld Z,Engels K,Samsell L,Baylis C

doi

10.1016/s0047-6374(01)00264-0

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

1293-301

issue

12

eissn

0047-6374

issn

1872-6216

pii

S0047-6374(01)00264-0

journal_volume

122

pub_type

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