Low-dose Angiotensin-converting Enzyme Research Articles

Low dose angiotensin converting enzyme inhibition and glomerular permselectivity in renal transplant recipients

In this study, we determined the fractional clearance of neutral polydisperse dextrans (theta D) and monodisperse dextran sulfate (theta DS) to describe glomerular size and charge selectivity in 25 renal transplant recipients with proteinuria. Thirteen were treated with low dose lisinopril for six months (group 1) and 12 patients without ACE inhibitor therapy formed group 2. Mean arterial blood pressure was stable (group 1, 112 +/- 4; group 2, 109 +/- 2 mm Hg at baseline and after 6 months) whereas creatinine clearance, glomerular filtration rate and renal plasma flow decreased nonsignificantly but were comparable at any time. Lisinopril treatment lowered filtration fraction (22 +/- 2 vs. 19 +/- 2%, P = 0.07) whereas no change was seen in group 2 (20 +/- 2%). The fractional protein excretion (mg urinary protein per day/ml creatinine clearance per day) was stable in group 1, but significantly increased in group 2. The same pattern was found for theta D larger than 56 A. theta DS was stable and consistently elevated in both groups at any time. We conclude that low dose ACE inhibitor treatment in proteinuric renal transplant recipients stabilizes glomerular size selectivity independently of its systemic hemodynamic effects.

Cardiac growth during high and low dose perindopril treatment in spontaneously hypertensive rats.

1. The effect of high and low dose angiotensin converting enzyme (ACE) inhibition and the contribution of bradykinin potentiation in this treatment on left and right ventricle weights and wall volume was investigated in immature spontaneously hypertensive rats (SHR). 2. Male SHR were treated from 7 to 11 weeks of age with perindopril (an ACE inhibitor) at a low dose of 0.1 mg/kg per day or a high dose of 1 mg/kg per day. Half the animals were also treated with a bradykinin receptor antagonist, HOE 140 (500 micrograms/kg per day). 3. After 4 weeks of treatment, hearts were arrested in diastole and perfusion fixed. The right and left ventricle plus septum were weighed, cut into 1 mm slices and volume was determined using the Cavalieri principle. 4. Low dose perindopril treatment did not significantly affect blood pressure in the SHR. High dose perindopril treatment maintained blood pressure at a level similar to Wistar-Kyoto (WKY) rats. 5. Growth of the right ventricle was not influenced by ACE inhibition. However, high dose treatment significantly lowered the left ventricle plus septum volume:bodyweight ratio (LV + S VOL:BWT) compared with control SHR (2.85 +/- 0.02 vs 3.36 +/- 0.08 mm3/g, respectively) to a level similar to the normotensive WKY rats (2.80 +/- 0.11 mm3/g). Similarly, low dose treatment significantly lowered the LV + S VOL:BWT ratio (2.89 +/- 0.09 mm3/g). HOE 140 treatment did not reverse the effect of ACE inhibition. Similar effects were observed on left ventricular weights. 6. ACE inhibition, independent of its blood pressure lowering effect, prevents the development of left ventricular hypertrophy in the SHR but does not influence growth of the right ventricle. This effect of ACE inhibition does not appear to be mediated by bradykinin potentiation.

75 Chronic low dose angiotensin converting enzyme inhibitor treatment improves cardiac function in stroke-prone spontaneously hypertensive rats by potentiation of endogenous bradykinin

Gohlke, Peter; Linz, Wolfgang; Schölkens, Bernward A.; Wiemer, G.; Kuwer, I.; S, ; Bartenbach, ; Schnell, A.; Unger, Thomas Author Information

Long-term low-dose angiotensin converting enzyme inhibitor treatment increases vascular cyclic guanosine 3',5'-monophosphate.

We investigated functional changes in aortic preparations of spontaneously hypertensive rats treated in utero and subsequently up to 20 weeks of age with the angiotensin converting enzyme (ACE) inhibitors ramipril (0.01 and 1 mg/kg per day) and perindopril (0.01 mg/kg per day). Early-onset treatment with the high dose of ramipril inhibited aortic ACE activity, prevented the development of hypertension, increased aortic vasodilator responses to acetylcholine (10(-8) to 10(-6) mol/L), decreased vasoconstrictor responses to norepinephrine (10(-8) mol/L), and increased aortic cyclic GMP content by 160%. Low-dose ramipril inhibited aortic ACE activity and attenuated the aortic vasoconstrictor response to norepinephrine but had no effect on blood pressure. Low-dose treatment with ramipril and perindopril resulted in a significant increase in aortic cyclic GMP content by 98% and 77%, respectively. Long-term coadministration of the bradykinin B2-receptor antagonist Hoe 140 abolished the ACE inhibitor-induced increase in aortic cyclic GMP. Our data demonstrate that long-term treatment with ACE inhibitors can alter vascular function of compliance vessels independently of the antihypertensive action. The increase in aortic cyclic GMP was due to bradykinin potentiating the action of the ACE inhibitors.

Spironolactone in congestive heart failure refractory to high-dose loop diuretic and low-dose angiotensin-converting enzyme inhibitor

Patients with severe congestive heart failure (New York Heart Association [NYHA] functional classes III–IV) often can tolerate only low doses of angiotensin-converting enzyme (ACE) inhibitors because pronounced hypotension caused by additional ACE inhibitor increments may decrease renal perfusion. The use of high-dose loop diuretics is currently advised to overcome diuretic resistance in refractory congestive heart failure (CHF). In a baseline controlled study, we evaluated 21 patients with diuretic resistance and evident fluid retention for the responses to 5 days of double drug therapy consisting of high-dose loop diuretic (10 mg oral bumetanide) in combination with the maximum tolerable dose of an ACE inhibitor (individualized to blood pressure and kidney function). Five patients (24%) showed a gross natriuresis and reduction in excess weight >25% in response to this therapy. The remaining 16 patients (76%) with insufficient responses (i.e., <25% reduction in excess weight) subsequently received 100 mg spironolactone once a day for 7 days in addition to the double therapy. Spironolactone coadministration was highly effective in 13 of 16 patients (81%). Marked natriuresis and diuresis were achieved within the next week of treatment, and CHF symptoms regressed or disappeared. The clinical course was similar in the bumetanide-ACE inhibitor and the bumetanide-ACE inhibitor-spironolactone treatment (triple therapy) groups. Plasma aldosterone was significantly higher (p < 0.05) in the patients who needed spironolactone. The 3 patients who were considered refractory to triple therapy exhibited the highest baseline plasma aldosterone concentrations. In the 13 patients who responded to spironolactone addition, hyperkalemia and azotemia did not occur during the 7 days of treatment, although 1 patient in the spironolactone treatment group developed reversible hyperkalemia and azotemia due to dehydration and decreased effective circulating volume after 8 days of treatment. Plasma aldosterone showed an inverse relation with urinary Na + K + ratio in 24-hour urine samples. Thus, coadministration of spironolactone was shown to be effective in managing CHF refractory to combination therapy with high doses of a loop diuretic and low doses of an ACE inhibitor. The urinary Na + K + ratio appears to be a useful and inexpensive indicator for determining the optimal spironolactone dose.

Blood pressure responses to low-dose oral ester or intravenous diacid angiotensin converting enzyme inhibitors

Blood pressure responses to low-dose oral ester or intravenous diacid angiotensin converting enzyme inhibitors

Discrepancy between first—dose converting enzyme inhibition at rest and subsequent inhibition during exercise in chronic heart failure

Low-dose angiotensin-converting enzyme inhibition is thought to completely block the renin-angiotensin system. This study examined the hemodynamic and hormonal responses to initial low- and higher dose converting-enzyme inhibitor (lisinopril or captopril) at rest compared with the response during subsequent chronic therapy while treadmill exercise testing was performed in nine patients with chronic heart failure. At rest, similar changes in systemic arterial pressure, plasma renin activity, and plasma aldosterone concentration were found with initial low and higher doses. However, after at least 4 weeks of therapy, dose-dependent increases in plasma renin activity and decreases in plasma aldosterone concentration were noted during exercise without significant differences in exercise systemic arterial pressure or heart rate. This discrepancy suggests that initial low-dose converting enzyme inhibition does completely block the enzyme, but higher dose therapy is required for complete blockade during subsequent exercise in chronic heart failure.

Relation of renal hemodynamics to angiotensin II in renal hilar lymph of the dog.

ARTICLESRelation of renal hemodynamics to angiotensin II in renal hilar lymph of the dogMD Bailie, R Loutzenhiser, and S MoyerMD Bailie, R Loutzenhiser, and S MoyerPublished Online:01 May 1972https://doi.org/10.1152/ajplegacy.1972.222.5.1075MoreSectionsPDF (915 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByAutoregulationRenal Circulation and Blockade of the Renin-Angiotensin SystemHypertension, Vol. 26, No. 4Spironolactone in congestive heart failure refractory to high-dose loop diuretic and low-dose angiotensin-converting enzyme inhibitorThe American Journal of Cardiology, Vol. 71, No. 3Efficacy of low-dose captopril in addition to furosemide and spironolactone in patients with decompensated liver disease during blunted diuresisJournal of Hepatology, Vol. 15, No. 1-2Renal perfusion and functionThe American Journal of Medicine, Vol. 84, No. 4Renal perfusion and functionThe American Journal of Medicine, Vol. 84Preservation of glomerular filtration rate in human heart failure by activation of the renin-angiotensin system.Circulation, Vol. 74, No. 4The effect of a converting enzyme inhibitor on autoregulation and intrarenal distribution of glomerular filtration in the ratActa Physiologica Scandinavica, Vol. 124, No. 4Effect of the protease inhibitor aprotinin on renal hemodynamics in the pig.Hypertension, Vol. 7, No. 1Contribution of the renin-angiotensin system to the control of intrarenal hemodynamicsKidney International, Vol. 25, No. 6Renal Plasma and Blood FlowAngiotensin as a Determinant of Renal Perfusion and FunctionGlomerular and renal hemodynamics during converting enzyme inhibition (SQ20,881) in the dog.Hypertension, Vol. 1, No. 4Lymphatic network of kidney II. Effect of diuretics on intrarenal renin releaseUrology, Vol. 12, No. 6Impaired Autoregulation of Blood Flow and Glomerular Filtration Rate in the Isolated Dog Kidney Depleted of ReninCirculation Research, Vol. 35, No. 3Acute renal failure in obstetric septic shockAmerican Journal of Obstetrics and Gynecology, Vol. 117, No. 1Autoregulation of Renal Blood Flow in Rabbits Immunized with Angiotensin II8 July 2009 | Scandinavian Journal of Clinical and Laboratory Investigation, Vol. 31, No. 1 More from this issue > Volume 222Issue 5May 1972Pages 1075-1078 Copyright & PermissionsCopyright © 1972 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1972.222.5.1075PubMed4336710History Published online 1 May 1972 Published in print 1 May 1972 Metrics