Effects of acute and chronic blockade of neutral endopeptidase with Sch 34826 on NaCl-sensitive hypertension in spontaneously hypertensive rats.

Abstract

We have previously demonstrated that dietary NaCl supplementation is associated with increased circulating atrial natriuretic peptide (ANP) levels in Wistar-Kyoto (WKY) rats but not in spontaneously hypertensive rats (SHR), and that replacement with exogenous ANP prevents NaCl-sensitive hypertension in NaCl-sensitive SHR (SHR-S). The current study tested the hypothesis that chronic administration of the neutral endopeptidase (NEP) inhibitor Sch 34826 prevents NaCl sensitive hypertension in SHR-S by increasing endogenous ANP. Male SHR-S received Sch 34826 (90 mg/kg/day) or vehicle by gavage for 4 weeks beginning immediately before the initiation of 1% or 8% NaCl diets at age 7 weeks. Sch 34826 prevented the increase in arterial pressure in response to 8% NaCl in SHR-S, but had no effect on blood pressure in 1% NaCl fed SHR-S; plasma ANP levels were increased by 63 and 68% in the 1% and 8% NaCl groups, respectively, in response to Sch 34826. To examine the mechanism(s) of the antihypertensive effect of Sch 34826 in NaCl-supplemented SHR-S, a single dose (90 mg/kg) of Sch 34826 or vehicle was administered by gavage to SHR-S that had consumed 1% or 8% NaCl diets for 3 weeks. Sch 34826 abolished the NaCl-induced increase in blood pressure 3 h after treatment in 8% NaCl fed SHR-S, but had no effect in SHR-S fed the 1% NaCl diet. This effect was associated with increased urine volume and urinary sodium, ANP, and cyclic GMP in 8% NaCl fed SHR-S.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: H Jin, C Mathews, Y F Chen, R Yang, J M Wyss, P Esunge, S Oparil
• Journal: American journal of hypertension (Am J Hypertens) Vol. 5 Issue 4 Pt 1 Pg. 210-8 (Apr 1992) ISSN: 0895-7061 [Print] United States
• PMID: 1318053 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Analgesics
• Dioxolanes
• Dipeptides
• Protease Inhibitors
• Sch 34826
• Sodium Chloride
• Atrial Natriuretic Factor
• Sodium
• Cyclic GMP

Topics

• Administration, Oral
• Analgesics (pharmacology)
• Animals
• Atrial Natriuretic Factor (urine)
• Blood Pressure (drug effects, physiology)
• Cyclic GMP (urine)
• Dioxolanes (pharmacology)
• Dipeptides (pharmacology)
• Hypertension (chemically induced, physiopathology, urine)
• Male
• Protease Inhibitors (pharmacology)
• Rats
• Rats, Inbred SHR (physiology)
• Rats, Inbred WKY
• Sodium (urine)
• Sodium Chloride (administration & dosage, adverse effects)