Excretory responses to renal nerve stimulation during inhibition of neutral metalloendopeptidase and angiotensin-converting enzyme in the rat

Raffaello Golin, Giuseppe Protasoni, Paulien Wjinmaalen, Carla Sala, Angela Monopoli, Carlo Casati, Alberto Zanchetti, Andrea Stella

Research output: Contribution to journalArticle

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Abstract

To evaluate the interaction between renal nerves, the atrial natriuretic peptide (ANP), and the renin-angiotensin system (RAS), electrical stimulation of renal nerves was performed in spontaneously hypertensive rats (SHR) and in their normotensive controls, Wistar Kyoto rats (WKY), before and after pharmacologic treatment with (a) a neutral endopeptidase inhibitor (NEP-i) to enhance the intrarenal ANP activity; (b) an ACE inhibitor (ACE-i) to block RAS: (c) both NEP-i and ACE-i; and (d) the vehicle of the drugs. Renal nerve stimulation did not change arterial pressure (AP) but reduced renal blood flow (RBF), glomerular filtration rate (GFR), and urinary sodium excretion (UNa+V) in both WKY and SHR. NEP-i treatment in WKY and SHR had no systemic or renal hemodynamic effects but increased GFR and urinary cyclic guanosine monophosphate (GMP) excretion: UNa+V increased (+2.78 ± 0.31 μEq/min) in WKY, whereas it did not change in SHR (+0.83 ± 0.79 μEq/min). In both strains, ACE-i treatment reduced AP, increased RBF, and did not change GFR and UNa+V. The combined treatment with NEP-i and ACE-i did not modify the natriuretic effect observed in NEP-i-treated WKY (+4.29 ± 1.25 μEq/min), but it elicited a natriuretic effect in SHR (+3.98 ± 1.29 μEq/min). Pharmacologic treatment did not change the hemodynamic and excretory responses to renal nerve stimulation in both WKY and SHR. In conclusion, NEP- i treatment increased UNa+V in normotensive rats without changing AP. In hypertensive rats, the natriuretic effect of NEP-i became evident only after block of RAS by ACE-i. Neither NEP-i nor ACE-i, even in combination, could modify the renal responses to sympathetic stimulation.

Original languageEnglish
Pages (from-to)665-671
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume28
Issue number5
DOIs
Publication statusPublished - 1996

Fingerprint

Metalloendopeptidases
Neprilysin
Peptidyl-Dipeptidase A
Protease Inhibitors
Inbred WKY Rats
Inbred SHR Rats
Angiotensin-Converting Enzyme Inhibitors
Kidney
Natriuretic Agents
Renin-Angiotensin System
Glomerular Filtration Rate
Arterial Pressure
Renal Circulation
Atrial Natriuretic Factor
Hemodynamics
Cyclic GMP
Electric Stimulation
Sodium

Keywords

  • Atrial natriuretic peptide
  • Neutral metalloendopeptidase
  • Renal nerves
  • Renin angiotensin system
  • SHR
  • Urinary sodium excretion

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Excretory responses to renal nerve stimulation during inhibition of neutral metalloendopeptidase and angiotensin-converting enzyme in the rat. / Golin, Raffaello; Protasoni, Giuseppe; Wjinmaalen, Paulien; Sala, Carla; Monopoli, Angela; Casati, Carlo; Zanchetti, Alberto; Stella, Andrea.

In: Journal of Cardiovascular Pharmacology, Vol. 28, No. 5, 1996, p. 665-671.

Research output: Contribution to journalArticle

Golin, Raffaello ; Protasoni, Giuseppe ; Wjinmaalen, Paulien ; Sala, Carla ; Monopoli, Angela ; Casati, Carlo ; Zanchetti, Alberto ; Stella, Andrea. / Excretory responses to renal nerve stimulation during inhibition of neutral metalloendopeptidase and angiotensin-converting enzyme in the rat. In: Journal of Cardiovascular Pharmacology. 1996 ; Vol. 28, No. 5. pp. 665-671.
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AU - Wjinmaalen, Paulien

AU - Sala, Carla

AU - Monopoli, Angela

AU - Casati, Carlo

AU - Zanchetti, Alberto

AU - Stella, Andrea

PY - 1996

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N2 - To evaluate the interaction between renal nerves, the atrial natriuretic peptide (ANP), and the renin-angiotensin system (RAS), electrical stimulation of renal nerves was performed in spontaneously hypertensive rats (SHR) and in their normotensive controls, Wistar Kyoto rats (WKY), before and after pharmacologic treatment with (a) a neutral endopeptidase inhibitor (NEP-i) to enhance the intrarenal ANP activity; (b) an ACE inhibitor (ACE-i) to block RAS: (c) both NEP-i and ACE-i; and (d) the vehicle of the drugs. Renal nerve stimulation did not change arterial pressure (AP) but reduced renal blood flow (RBF), glomerular filtration rate (GFR), and urinary sodium excretion (UNa+V) in both WKY and SHR. NEP-i treatment in WKY and SHR had no systemic or renal hemodynamic effects but increased GFR and urinary cyclic guanosine monophosphate (GMP) excretion: UNa+V increased (+2.78 ± 0.31 μEq/min) in WKY, whereas it did not change in SHR (+0.83 ± 0.79 μEq/min). In both strains, ACE-i treatment reduced AP, increased RBF, and did not change GFR and UNa+V. The combined treatment with NEP-i and ACE-i did not modify the natriuretic effect observed in NEP-i-treated WKY (+4.29 ± 1.25 μEq/min), but it elicited a natriuretic effect in SHR (+3.98 ± 1.29 μEq/min). Pharmacologic treatment did not change the hemodynamic and excretory responses to renal nerve stimulation in both WKY and SHR. In conclusion, NEP- i treatment increased UNa+V in normotensive rats without changing AP. In hypertensive rats, the natriuretic effect of NEP-i became evident only after block of RAS by ACE-i. Neither NEP-i nor ACE-i, even in combination, could modify the renal responses to sympathetic stimulation.

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