Renal Effects of Perindoprilat, an Angiotensin-Converting Enzyme Inhibitor, in the Anesthetized Dog

Schmidt, M; Krieger, Jean-Paul; Devissaguet, M; Imbs, Jean-Louis

doi:10.1097/00005344-198902000-00017

Cited by 6 publications

(4 citation statements)

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“…Under these conditions it is unlikely that the renin-angiotensin system was exerting a great degree of tonic influence over sodium reabsorption. Indeed, previous studies in salt-replete dogs using either ACE inhibitors (Schmidt et al, 1989) or saralasin (Lohmeier et al, 1977), have also found that when blood pressure is reduced, these agents do not cause a significant diuresis/natriuresis. Moreover, in anaesthetized salt-replete guinea-pigs (Amrani et al, 1991), and volume-expanded rats (Fenoy et al, 1991), the AT, receptor antagonist, losartan, reduces blood pressure but does not cause a significant diuresis.…”

Section: Discussionmentioning

confidence: 93%

Role of angiotensin AT₁ and AT₂ receptors in mediating the renal effects of angiotensin II in the anaesthetized dog

Clark

Robertson

Drew

1993

British J Pharmacology

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1 Experiments were performed using the selective AT, receptor antagonist, GRI 17289, and the selective AT2 receptor antagonist, PD123177, to assess the relative importance of AT, versus AT2 receptors in mediating the renal effects of angiotensin II (AII) in vivo, in salt-replete pentobarbitoneanaesthetized dogs.2 The AT, receptor antagonist, GRI17289 (0.5 mg kg-' + 1 g kg-min-', i.v.), caused renal vasodilatation, characterized by a mean increase of 21 ± 5% in renal blood flow, 45 min post-dose. GRI 17289 also caused a fall in mean blood pressure (12 ± 4%), but despite this, sodium and urine excretion were not reduced. Indeed, there was a tendency for urine output and sodium excretion to increase, although the changes were not statistically significant. GRI 17289 caused a reduction in plasma aldosterone levels (-35 + 16%) 45 min post-dose, despite increasing plasma renin activity (+ 173 ± 42%). In contrast to GRI 17289, the AT2 receptor antagonist, PD123177 (20 fg kg-1 min-' intra-renal artery; i.r.a.) caused no significant change in blood pressure, renal blood flow, or sodium and urine excretion, indicating that the renal effects of endogenous AII in these salt-replete animals are mediated predominantly by AT, receptors. 3 Intra-renal artery infusion of AII (1-300 ng kg-' min-') caused dose-related renal vasoconstriction, and decreases in urine output, sodium excretion, fractional excretion of sodium, and glomerular filtration rate (GFR). The AT, receptor antagonist, GRI 17289 (0.5 mg kg-'+ 1 pg kg' min- ', i.v.) antagonized these renal effects of AII, causing 15-38 fold rightward displacements of mean doseresponse curves for these parameters. In contrast, PD123177 (20 fg kg-min-', i.r.a.) failed to antagonize the renal haemodynamic and excretory effects of lower doses of All (1-10 ng kg-' minm-, i.r.a.). However, at higher doses of AII (30-300 ng kg-l min-', i.r.a.), while PD123177 still failed to antagonize the effects of the peptide on urine output, sodium excretion and GFR, it did cause a small, but significant, degree of inhibition of All-induced renal vasoconstriction. In addition, at a higher dose (50 jig kg-' min-, i.r.a.), PD123177 caused a greater degree of antagonism of AII-induced renal vasoconstriction, while renal excretory responses to All remained unaffected. 4 This study shows that the renal haemodynamic and excretory effects of AII in salt-replete anaesthetized dogs are mainly mediated by angiotensin AT, receptors. However, the inhibitory effect of PD123177 on renal vasoconstrictor responses to high doses of AII, raises the possibility that functionally important AT2 receptors are present in the canine renal vasculature.

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Section: Discussionmentioning

confidence: 93%

Role of angiotensin AT₁ and AT₂ receptors in mediating the renal effects of angiotensin II in the anaesthetized dog

Clark

Robertson

Drew

1993

British J Pharmacology

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“…The ACEI induce changes in renal function, especially in renal hemodynamics. In healthy dogs, acute and chronic administrations of ACEI typically result in increased effective renal plasma flow (ERPF), no change or increase in glomerular filtration rate (GFR), and decrease in filtration fraction, as shown for captopril (DeForrest et al, 1982;Kastner et al, 1982;Seymour et al, 1993;Heller et al, 1997), enalapril (Zimmerman et al, 1990;Omoro et al, 1999), ramipril (Persson et al, 1989;Kaczmarczyk et al, 1996 3 ), imidapril (Nishiyama et al, 1992), and perindopril (Schmidt et al, 1989), or their active metabolites. No change in GFR and 4 ERPF was induced in healthy dogs by benazepril treatment (Brands et al, 1993).…”

Section: Effect Of Acei On Raas and Renal Function In Healthy Conditionsmentioning

confidence: 99%

“…, 1996), imidapril (Nishiyama et al. , 1992), and perindopril (Schmidt et al. , 1989), or their active metabolites.…”

Section: Effect Of Acei On Raas and Renal Function In Healthy Conditionsmentioning

confidence: 99%

Angiotensin‐converting enzyme inhibitors in the therapy of renal diseases

Lefebvre

Toutain

2004

Vet Pharm & Therapeutics

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Renal diseases, especially chronic renal failure (CRF), are common in canine and feline medicine. The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in these conditions in the development of renal lesions and the progression of kidney dysfunction. Angiotensin-converting enzyme inhibitors (ACEI) are currently considered as the most efficient agents in therapeutic strategies. The benefit of an ACEI treatment can be explained by at least three mechanisms: ACEI limit systemic and glomerular capillary hypertension, have an antiproteinuric effect, and retard the development of glomerulosclerosis and tubulointerstitial lesions. These effects have been studied in dogs and cats, and there is now some evidence to support the recommendation of ACEI therapy in dogs and cats with CRF. Nevertheless the prescription of ACEI in such patients should take into account the potential influence of renal impairment on ACEI disposition, and adverse effects on the renal function itself (especially hypotension and acute reductions in glomerular filtration rate). The risk of drug interaction with diuretics, nonsteroidal anti-inflammatory drugs and anesthetics, should not be overestimated. Furthermore, hypotension may occur in patients on a low sodium diet.

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“…Changes in renal hemodynamics following acute or chronic administration of perindopril have been studied in normotensive and hypertensive animals. With a single dose perindopril decreased renal vascular resistance, increasing renal blood flow, whatever the blood pressure level or the sodium balance (37, 63,128,136). In the normotensive rat, perindopril (0.1 mg/kg p.0.)…”

Section: Kidneymentioning

confidence: 99%

Perindopril

Atkinson¹

1992

Cardiovascular Drug Reviews

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Renal Effects of Perindoprilat, an Angiotensin-Converting Enzyme Inhibitor, in the Anesthetized Dog

Cited by 6 publications

References 0 publications

Role of angiotensin AT₁ and AT₂ receptors in mediating the renal effects of angiotensin II in the anaesthetized dog

Role of angiotensin AT₁ and AT₂ receptors in mediating the renal effects of angiotensin II in the anaesthetized dog

Angiotensin‐converting enzyme inhibitors in the therapy of renal diseases

Perindopril

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Renal Effects of Perindoprilat, an Angiotensin-Converting Enzyme Inhibitor, in the Anesthetized Dog

Cited by 6 publications

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Role of angiotensin AT1 and AT2 receptors in mediating the renal effects of angiotensin II in the anaesthetized dog

Role of angiotensin AT1 and AT2 receptors in mediating the renal effects of angiotensin II in the anaesthetized dog

Angiotensin‐converting enzyme inhibitors in the therapy of renal diseases

Perindopril

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Product

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Role of angiotensin AT₁ and AT₂ receptors in mediating the renal effects of angiotensin II in the anaesthetized dog

Role of angiotensin AT₁ and AT₂ receptors in mediating the renal effects of angiotensin II in the anaesthetized dog