Renal Effects of ACE Inhibition in Ovine Heart Failure: A Comparison of Intermittent and Continuous ACE Inhibition

Ma, Fei; Mt, Rademaker; Cm, Frampton; Espiner, E. A.; Yandle, Tim G.; A'Court, G; Ikram, Hamid

doi:10.1097/00005344-199010000-00015

Cited by 9 publications

(8 citation statements)

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“…Deterioration of renal function during ACE inhibition does not depend on intermittent or continuous ACE inhibition, as shown in ovine heart failure [37]. This may also apply to most patients with severe heart failure.…”

Section: Discussionmentioning

confidence: 73%

Comparison of captopril with enalapril in the treatment of heart failure: Influence on hemodynamics and measures of renal function

Osterziel

Dietz

Harder

et al. 1992

Cardiovasc Drug Ther

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Twenty-nine patients with severe heart failure (NYHA III) were randomly assigned to receive therapy with an angiotensin converting enzyme inhibitor (ACE inhibitor), either captopril or enalapril. The mean daily dosage of captopril was 56 +/- 5 mg and of enalapril 9.5 +/- 0.4 mg. After a mean of 8 +/- 1 days, the influence of both ACE inhibitors on hemodynamics and renal function was compared. The mean arterial pressure in the group treated with captopril (Group A) fell by 9 +/- 3 mmHg (p less than 0.01), and in the group treated with enalapril (Group B) it fell by 12 +/- 3 mmHg (p less than 0.001). The difference between the groups was not significant. Heart rate decreased in both groups; however, the change was significant (p less than 0.05) only in patients treated with enalapril (-11 +/- 3 bpm in Group B vs. -7 +/- 4 bpm in Group A). Stroke volume index increased by 6 +/- 3 ml/m2 in Group A (p less than 0.05) vs. 10 +/- 2 ml/m2 in Group B (p less than 0.01). The increase in stroke volume index was not significantly different between the two groups. Mean decreases in pulmonary artery and right atrial pressure were also comparable in both groups. Thus, hemodynamic improvements were similar during therapy with either captopril or enalapril. Serum sodium and potassium before therapy were 137 +/- 1 mmol/l and 4.1 +/- 0.1 mmol/l, respectively, in group A and 139 +/- 1 mmol/l and 4.0 +/- 0.1 mmol/l, respectively, in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 73%

Comparison of captopril with enalapril in the treatment of heart failure: Influence on hemodynamics and measures of renal function

Osterziel

Dietz

Harder

et al. 1992

Cardiovasc Drug Ther

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“…34 By contrast with these results, our previous studies in this severe HF model demonstrated a progressive decline in endogenous creatinine clearance with repeated doses of the ACE inhibitor captopril. 19 The beneficial renal hemodynamic effects of omapatrilat in this study may be mediated by local enhancement of ANP, BNP, or urodilatin levels within the kidney. 16,35 ANP increases efferent glomerular arteriolar tone, one mechanism by which GFR may be maintained in the current setting.…”

Section: Troughton Et Al Omapatrilat In Mild and Severe Heart Failurementioning

confidence: 68%

“…29,30 There have been concerns regarding the effects of ACE inhibitor on renal function in more severe grades of HF, particularly in diabetics, when high diuretic doses are required, or if there is concomitant renovascular disease. 19,20 Vasopeptidase inhibitors act on both ACE and neutral endopeptidase, producing simultaneous reduction in Ang II formation and augmentation of circulating cardiac peptide levels. 10 As has been demonstrated with omapatrilat and other agents, synergistic dual inhibition can produce potent antihypertensive actions, beneficial renal effects, and other potential benefits.…”

Section: Troughton Et Al Omapatrilat In Mild and Severe Heart Failurementioning

confidence: 99%

“…14 -17 A major potential benefit of vasopeptidase inhibitors in the treatment of HF is preservation or even enhancement of renal function 15,18 compared with ACE inhibitor therapy alone. 15,19,20 Omapatrilat has demonstrated potent hypotensive effects across the spectrum of renin and volumedependent models of hypertension. 21 Early results in HF suggest beneficial hemodynamic and urinary effects 14,18,22 mediated by synergistic ACE and neutral endopeptidase inhibition.…”

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confidence: 99%

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Beneficial Renal and Hemodynamic Effects of Omapatrilat in Mild and Severe Heart Failure

et al. 2000

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Abstract-Omapatrilat is a member of the new drug class of vasopeptidase inhibitors that may offer benefit in the treatment of heart failure (HF) through simultaneous inhibition of angiotensin-converting enzyme and neutral endopeptidase. We examined the effects of omapatrilat in a placebo-controlled crossover study using a pacing model of HF. Seven sheep were paced sequentially at 180 bpm (mild HF) and then 225 bpm (severe HF) for 7 days each. Omapatrilat (0.005 mg/kg) or vehicle was administered by intravenous bolus on days 4 to 7 of each paced period. Omapatrilat lowered mean arterial and left atrial pressure and increased cardiac output acutely and chronically in both mild and severe HF (PϽ0.01 for all). Plasma atrial and brain natriuretic peptide and cGMP levels were stable acutely (PϭNS), while brain natriuretic peptide increased after repeated dosing in severe HF (PϽ0.05). Plasma renin activity rose, whereas angiotensin II and aldosterone levels fell after acute and repeated dosing in both states (PϽ0.01 for all). Omapatrilat increased urinary sodium excretion by day 7 in both mild and severe HF (PϽ0.05). Effective renal plasma flow and glomerular filtration rate increased or were stable after omapatrilat in mild and severe HF after both acute and repeated dosing. Omapatrilat exhibited pronounced acute and sustained beneficial hemodynamic and renal effects in both mild and severe heart failure. (Hypertension. 2000;36:523-530.)

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“…Packer et al 12 found that the longer acting ACE inhibitor enalapril (at a dose of 20 mg orally twice a day) compromised renal function more than captopril (50 mg orally three times daily), which had a shorter duration of action on BP. On the other hand, in a model of ovine heart failure, Fitzpatrick et al 13 compared the effects of intermittent and continuous inhibition on renal function. The action duration of ACE inhibition per se did not appear in their study to be a major determinant of renal impairment.…”

Section: T He Intrarenal Renin-angiotensin System (Ras)mentioning

confidence: 99%

Continuous versus intermittent angiotensin converting enzyme inhibition in renal hypertensive rats.

et al. 1993

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Converting enzyme inhibitors impair renal function of the kidney beyond a stenosis of the renal artery in humans and induce histologlcal lesions in the clipped kidney of renal hypertensive rats. In two-kidney, one clip hypertensive rats, we compared the time course and magnitude of the biochemical effects of angiotensin converting enzyme inhibition on the plasma renin-angiotensin system, cardiac hypertrophy, renal lesions, and 24-hour blood pressure decrease induced by either intermittent angiotensin converting enzyme inhibition administration (benazepril PO, 10 mg/kg once a day, n=93) or continuous administration (benazeprilat, 3 mg/kg per day via osmotic pumps, n=92). Control rats (n=91) received the drug vehicle intermittently or continuously. Mortality was significantly reduced by both intermittent (n=3/93) and continuous (n=3/92) inhibition compared with controls (n=18/91) (P<.001). Changes in the plasma renin-angiotensin system and blood pressure were parallel. A continuous suppression of the activity of the plasma renin-angiotensin system was associated with a 24-hour decrease in blood pressure with continuous inhibition, whereas intermittent inhibition induced a similar fall in blood pressure only for the first hours after gavage. Heart weight (5.12±0.12, 3.98±0.09, 4_32±0.12 g/kg in controls [n=8], continuous inhibition [n=18], and intermittent inhibition [n=18], respectively) was significantly reduced to the same extent by both treatments (P<.0001), and clipped kidney weight (3.28±0.11, 1.83±0.12, 2.20±0.15 g/kg in controls [n=8], continuous inhibition [n=18], and intermittent inhibition [n=18], respectively) was significantly reduced in both groups of treated rats (P<.0001). After removal of the undipped kidney, plasma creatinine was significantly increased in both treatment groups (7 > <.0001) compared with nephrectomized hypertensive control rats but to a significantly greater extent in the continuously inhibited rats (117±39, 317±8, 260±8 /u.mol/L in controls [n=8], continuous inhibition [n=18], and intermittent inhibition [n = 18]; P<.0001). Therefore, changes in blood pressure and the plasma renin-angiotensin system were parallel after either continuous or intermittent inhibition. It was possible to decrease blood pressure continuously during 24 hours only with continuous inhibition. Both treatments reduced heart weight to a similar extent. Damage to the clipped kidney, as revealed by elevated plasma creatinine levels after nephrectomy of the undipped kidney, was slightly reduced but not avoided by the intermittent inhibition. (Hypertension 1993^2:188-196) KEY WORDS • hypertension, renovascular • angiotensin converting enzyme inhibition • angiotensin II • rat studies T he intrarenal renin-angiotensin system (RAS) plays a major role in sustaining glomerular filtration rate in situations in which the system has been stimulated, such as sodium depletion, renal artery stenosis, or congestive heart failure.1 ' 2 Under these circumstances, angiotensin I converting enzyme (ACE) inhibition impairs rena...

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Renal Effects of ACE Inhibition in Ovine Heart Failure: A Comparison of Intermittent and Continuous ACE Inhibition

Cited by 9 publications

References 0 publications

Comparison of captopril with enalapril in the treatment of heart failure: Influence on hemodynamics and measures of renal function

Comparison of captopril with enalapril in the treatment of heart failure: Influence on hemodynamics and measures of renal function

Beneficial Renal and Hemodynamic Effects of Omapatrilat in Mild and Severe Heart Failure

Continuous versus intermittent angiotensin converting enzyme inhibition in renal hypertensive rats.

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