Atrial natriuretic factor-potentiating and antihypertensive activity of SCH 34826. An orally active neutral metalloendopeptidase inhibitor.

Sybertz, Edmund J.; Chiu, Peter; Vemulapalli, Subbarao; Watkins, Robert W.; Haslanger, Martin F.

doi:10.1161/01.hyp.15.2.152

Cited by 63 publications

(24 citation statements)

References 31 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Systemic administration of phosphoramidon, which inhibits NEP-24.11 (a major kininase in the nephron), caused urinary kinin excretion to double; diuresis increased by 15% and natriuresis by 37% (290). Although these data support the hypothesis that increased kinins in the nephron heighten intrarenal control of water and electrolyte excretion, it is also possible that the effect of phosphoramidon is mediated by blocking hydrolysis of other peptides such as ANF (279).…”

Section: Kinins In Regulation Of Water and Electrolyte Excretionmentioning

confidence: 80%

The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function

Carretero¹,

Yang²,

Rhaleb³

2005

Hypertension

View full text Add to dashboard Cite

Section: Kinins In Regulation Of Water and Electrolyte Excretionmentioning

confidence: 80%

The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function

Carretero¹,

Yang²,

Rhaleb³

2005

Hypertension

View full text Add to dashboard Cite

“…Attempts to prolong the bioavailability of ANP in vivo have included ANP clearance receptor blockade, and inhibition of NEP. Studies using NEP inhibitors in vivo have demonstrated an increase in the half-life and natriuretic effect of exogenous ANP (Lafferty et al, 1989;Sybertz et al, 1990a). This is a specific effect since ANP antisera blocks the activity of NEP inhibitors (Shepperson et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Neutral endopeptidase (NEP) inhibition in rats with established pulmonary hypertension secondary to chronic hypoxia

Thompson

Sheedy

Morice

1994

British J Pharmacology

View full text Add to dashboard Cite

1Atrial natriuretic peptide (ANP) causes vasorelaxation in the pulmonary vasculature. ANP levels are elevated in conditions characterized by pulmonary hypertension and it has been hypothesized that ANP may be autoregulatory in the pulmonary circulation. 2 One route of ANP metabolism in vivo is by the action of the enzyme neutral endopeptidase (NEP). We have studied the effects of the NEP inhibitor, SCH 42495, in rats with established pulmonary hypertension secondary to chronic hypoxia. 3 Rats (n = 32) were divided into 4 groups. Normoxic controls were kept in air for 10 days (NClO) and all other animals were placed in a normobaric hypoxic chamber (Fi 02 10%). Chronic hypoxic controls were studied at 10 days (CHC10). After 10 days hypoxia the two remaining groups received oral treatment for a further 10 days, consisting of either SCH 42495 (30 mg kg-', twice daily CHT20) or methyl cellulose vehicle (0.4%, twice daily, CHV20). 4 Animals were anaesthetized and blood collected for measurement of plasma ANP. Hearts were dissected and ventricles weighed and the histology of the pulmonary vasculature examined. 5 CHClO rats had significant right ventricular hypertrophy (0.53 ± 0.08) and pulmonary vascular remodelling (29.0 0.01%) and had gained significantly less body weight (33.2 ± 5.5 g) than NC1O rats (0.31 ± 0.04, 10.9 0.01%, and 59.2 ± 11.9 g respectively). CHC1O rats had significantly elevated plasma ANP levels (58.4 ± 9.9 pM) compared with NClO rats (23.9 ± 32 pM). Treatment with SCH 42495 caused a significant reduction in pulmonary vascular remodelling (25.0 ± 0.01%) and right ventricular hypertrophy (0.52 ± 0.09) in CHT20 rats compared with CHV20 controls (33.0 ± 0.02% and 0.61 ± 0.09 respectively). Pulmonary vascular remodelling was also significantly lower in CHT20 rats than CHC1O animals. 6 Thus, short term inhibition of NEP causes regression of established pulmonary vascular remodelling and may be a useful therapeutic strategy in pulmonary hypertension.

show abstract

“…21 It would appear that studies on the long-term effects of ANF metabolic inhibitors are essential to determine their importance and effectiveness as therapeutic tools for the treatment of cardiovascular diseases such as congestive heart failure and hypertension. Indeed, in a recently published report by Sybertz et al, 22 an orally active NEP-I was shown to reduce mean arterial pressure in spontaneously hypertensive rats by 30-40 mm Hg after 5 days of administration. In contrast, the NEP-I had no effect on mean arterial pressure after the first 4 hours of administration.…”

Section: Editorial Comment Inhibitors Of Anf Metabolismmentioning

confidence: 97%

Inhibitors of ANF metabolism. Potential therapeutic agents in cardiovascular disease.

Granger

1990

Circulation

View full text Add to dashboard Cite

Atrial natriuretic factor-potentiating and antihypertensive activity of SCH 34826. An orally active neutral metalloendopeptidase inhibitor.

Abstract: T he atrial natriuretic factors (ANFs) are vasodilator, natriuretic, and diuretic peptides with a potential role in the physiological regulation of blood pressure and fluid and electrolyte homeostasis.

Cited by 63 publications

References 31 publications

The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function

The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function

Neutral endopeptidase (NEP) inhibition in rats with established pulmonary hypertension secondary to chronic hypoxia

Inhibitors of ANF metabolism. Potential therapeutic agents in cardiovascular disease.

Contact Info

Product

Resources

About