Humoral and Renal Effects of MK-421 (Enalapril) in Hypertensive Subjects

Leeuw, Peter W. de; Hoogma, Roel P.L.M.; Soest, G. A. W. Van; Tchang, Pau T.; Birkenhäger, W. H.

doi:10.1097/00005344-198309000-00005

Cited by 24 publications

(8 citation statements)

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“…In agreement with previous reports (Atkinson et al 1979;Tarazi el al. 1980;de Leeuw et al 1983;Omvik & Lund-Johansen 1984), after 6 weeks of treatment extracellular fluid volumes were similar to those before drug administration. At this time proximal tubular sodium reabsorption might be still enhanced in view of the persisting increase in filtration fraction but it is probably fully compensated by a decrease in distal tubular sodium reabsorption secondary to late onset aldosterone suppression (Griffing et al 1982).…”

Section: Resultssupporting

confidence: 52%

“…This latter action is said to operate mainly in the long-term, but measurement of body fluids and sodium balance in hypertensive patients chronically treated with converting enzyme inhibitors have given conflicting results. Extracellular fluids and body weight are mostly unchanged (Sullivan et al 1979; Tarazi et al 1980;Wenting et al 1982;de Leeuw et al 1983;Omvik & Lund-Johansen 1984), plasma volume is actually increased (Sullivan et al 1979;Tarazi et al 1980;de Leeuw et al 1983) and in a few cases sodium balance is positive (Case et al 1978;Atlas et al 1979).…”

Section: Introductionmentioning

confidence: 99%

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Time Course of Changes in Blood Pressure, Aldosterone and Body Fluids During Enalapril Treatment: A Double‐blind Randomized Study vs Hydrochlorothiazide Plus Propranolol in Essential Hypertension

Semplicini

Rossi

Bongiovi

et al. 1986

Clin Exp Pharma Physio

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Aldosterone suppression is said to play a major role in the long term hypotensive efficacy of angiotensin converting enzyme inhibitors. However, in previous reports from other laboratories, plasma volume has been found mostly increased and sodium balance sometimes positive. The effects of the angiotensin converting enzyme inhibitor enalapril (10-40 mg/day, p.o., for 6 weeks) on blood pressure, body fluid volumes, renal function and plasma aldosterone were compared to those of hydrochlorothiazide (50 mg/day, p.o.) alone for 2 weeks and in association with propranolol (80-160 mg/day, p.o.) for 4 more weeks during a randomized double-blind parallel study in 14 essential hypertensives. Hydrochlorothiazide alone and in combination with propranolol induced slight and not significant change in either blood pressure and body fluids. The maximum hypotensive response to enalapril was achieved only after 2 weeks of continuous treatment possibly because after 1 week the hypotensive efficacy was lessened by a significant (P less than 0.05) fluid retention secondary to a transient and not significant fall in renal perfusion. At this time aldosterone was not significantly changed compared to pretreatment values. After 6 weeks on enalapril, blood pressure was significantly reduced, plasma aldosterone further but not significantly decreased and extracellular fluid volume was normal. These findings indicate that aldosterone suppression contributes to the blood pressure lowering effect of enalapril by offsetting the salt and water retention observed on starting treatment and due to direct vasodilation.

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Section: Resultssupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Time Course of Changes in Blood Pressure, Aldosterone and Body Fluids During Enalapril Treatment: A Double‐blind Randomized Study vs Hydrochlorothiazide Plus Propranolol in Essential Hypertension

Semplicini

Rossi

Bongiovi

et al. 1986

Clin Exp Pharma Physio

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“…Major changes in vagal tone apparently do not occur with ACEIs (Mancia et al, 1982;Millar et al, 1982;Warren et al, 1983) but regarding the sympathetic system, there are contradictory data in the literature. Thus a sympatho-inhibitory effect of ACEIs has been demonstrated in a number of experimental (Casellas et al, 1980;Antonaccio & Kerwin, 1981;Richer et al, 1983) and clinical (Imai et al, 1982;De Leeuw et al, 1983;Warren et al, 1983) studies but was not found by others (Mancia et al, 1982;Millar et al, 1982;Ibsen et al, 1983).…”

Section: Discussionmentioning

confidence: 90%

The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects.

Jf¹,

Berdeaux²,

Édouard³

et al. 1985

Brit J Clinical Pharma

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The effects of enalapril, 20 mg orally, on the responses to baroreflex activation and deactivation by respectively phenylephrine and nitroglycerin were investigated in normotensive subjects on a normal sodium diet, with simultaneous measurement of plasma renin activity (PRA), converting enzyme activity (PCEA), aldosterone and catecholamines. Enalapril, 4 h after administration, lowered artificial blood pressure without modifying heart rate and plasma catecholamines. PCEA was abolished, PRA increased and plasma aldosterone decreased. Enalapril (a) displaced to the left the baroreflex set‐point, (b) did not affect baroreflex sensitivity since the slopes of the RR‐ interval/systolic blood pressure regression lines remained unchanged during both activation and deactivation and (c) did not modify baroreflex efficacy since the maximal RR‐interval responses as well as the overall RR‐interval‐time products to identical blood pressure variations were not modified. Thus, enalapril induced a resetting of the baroreflex, which probably accounts for the lack of reflex tachycardia observed during the drug‐induced fall in blood pressure.

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“…With repeat daily dosing in normal volunteers, steady state concentrations were reached by the third day, and only a small accumulation factor was identified . Johnston et al (1983Johnston et al ( , 1984a and DeLeeuw et al (1983) have correlated serum enalaprilat levels, inhibition of converting enzyme, and blood pressure reduction reported that serum concentrations of enalapril were similar when the drug was administered during fasting or after a standard breakfast. By contrast, food has been shown to depress the absorption of captopril by about 50% (Kripalani et al, 1980).…”

Section: Dispositionmentioning

confidence: 99%

An overview of the clinical pharmacology of enalapril.

Rr¹,

Gómez²,

Jd³

et al. 1984

Brit J Clinical Pharma

106

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Enalapril maleate is a prodrug which when administered orally is hydrolysed to release the active converting enzyme inhibitor enalaprilat. Enalapril maleate is 60% absorbed and 40% bioavailable as enalaprilat. Both compounds undergo renal excretion without further metabolism. The functional half‐life for accumulation of enalaprilat is 11 h, and this is increased in the presence of a reduction in renal function. Inhibition of converting enzyme inhibition is associated with reductions in plasma angiotensin II and plasma aldosterone, and with increases in plasma renin activity and plasma angiotensin I. Acute and chronic effects have been reviewed. When given with hydrochlorothiazide, enalapril attenuates the secondary aldosteronism and ameliorates the hypokalaemia from diuretics. Both acutely and chronically in patients with essential hypertension, enalapril reduced blood pressure with a rather flat dose‐response curve. No evidence of a triphasic response such as seen with captopril has been demonstrated with enalapril, and blood pressure returns smoothly to pretreatment levels when the drug is abruptly discontinued. Once‐ or twice‐daily dosing gives similar results. The antihypertensive effects of enalapril are potentiated by hydrochlorothiazide. Haemodynamically, blood pressure reduction is associated with a reduced peripheral vascular resistance and an increase in cardiac output and stroke volume with little change in heart rate. Renal vascular resistance decreases, and renal blood flow may increase without an increase in glomerular filtration in patients with normal renal function. In patients with essential hypertension and glomerular filtration rates below 80 ml/min/m2, both renal blood flow and glomerular filtration rates may increase.

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Humoral and Renal Effects of MK-421 (Enalapril) in Hypertensive Subjects

Cited by 24 publications

References 0 publications

Time Course of Changes in Blood Pressure, Aldosterone and Body Fluids During Enalapril Treatment: A Double‐blind Randomized Study vs Hydrochlorothiazide Plus Propranolol in Essential Hypertension

Time Course of Changes in Blood Pressure, Aldosterone and Body Fluids During Enalapril Treatment: A Double‐blind Randomized Study vs Hydrochlorothiazide Plus Propranolol in Essential Hypertension

The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects.

An overview of the clinical pharmacology of enalapril.

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