title: Excretory responses to renal nerve stimulation during inhibition of neutral metalloendopeptidase and angiotensin-converting enzyme in the rat.
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 microEq/min) in WKY, whereas it did not change in SHR (+0.83 +/- 0.79 microEq/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 microEq/min), but it elicited a natriuretic effect in SHR (+3.98 +/- 1.29 microEq/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.
authors.affiliation: Istituto di Clinica Medica Generale e Terapia Medica, University of Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Golin
authors.forename: G
authors.initials: G
authors.lastname: Protasoni
authors.forename: P
authors.initials: P
authors.lastname: Wjinmaalen
authors.forename: C
authors.initials: C
authors.lastname: Sala
authors.forename: A
authors.initials: A
authors.lastname: Monopoli
authors.forename: C
authors.initials: C
authors.lastname: Casati
authors.forename: A
authors.initials: A
authors.lastname: Zanchetti
authors.forename: A
authors.initials: A
authors.lastname: Stella
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology; D004558:Electric Stimulation; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000294:innervation*; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D010654:Phenylbutyrates / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013141:Spiro Compounds / Q000494:pharmacology; D014563:Urodynamics / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D010654:Phenylbutyrates; D011480:Protease Inhibitors; D013141:Spiro Compounds; C056109:SCH 33861; C062344:SCH 32615; D009320:Atrial Natriuretic Factor; D015260:Neprilysin