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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2008.08.030 Byline: Daphne T. Hsu (a), Seema Mital (a), Chitra Ravishankar (b), Renee Margossian (c), Jennifer S. Li (d), Lynn A. Sleeper (e), Richard V. Williams (f), Jami C. Levine (c), Brian W. McCrindle (g), Andrew M. Atz (h), Darlene Servedio (a), Lynn Mahony (i) Abstract: Angiotensin converting enzyme (ACE) inhibitors are known to improve clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology show abnormalities in ventricular function as well as poor growth. The ability of an ACE inhibitor to preserve ventricular function and improve growth in these infants is unknown. Author Affiliation: (a) Columbia University, New York, NY (b) Children's Hospital of Philadelphia, Philadelphia, PA (c) Children's Hospital Boston, Boston, MA (d) Duke University, Durham, NC (e) New England Research Institutes, Watertown, MA (f) Primary Children's Medical Center, Salt Lake City, UT (g) Hospital for Sick Children, Toronto, Ontario, Canada (h) Medical University of South Carolina, Charleston, SC (i) University of Texas at Southwestern Medical Center, Dallas, TX Article History: Received 18 July 2008; Accepted 12 August 2008 Article Note: (footnote) Trial Registration #: NCT00113087., Funded by the National Heart, Lung, and Blood Institute (Bethesda, MD), National Institutes of Health (Bethesda, MD)/Department of Health and Human Services (Washington, DC)., Supported by U01 grants from the National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057)., Dr. J. Michael DiMaio served as guest editor for this manuscript.

Acute physiological hyperinsulinemia increases skeletal muscle capillary blood volume (CBV), presumably to augment glucose and insulin delivery. We hypothesized that insulin-mediated changes in CBV are impaired in type 2 diabetes mellitus (DM) and are improved by angiotensin-converting enzyme inhibition (ACE-I). Zucker obese diabetic rats (ZDF, n = 18) and control rats (n = 9) were studied at 20 wk of age. One-half of the ZDF rats were treated with quinapril (ZDF-Q) for 15 wk prior to study. CBV and capillary flow in hindlimb skeletal muscle were measured by contrast-enhanced ultrasound (CEU) at baseline and at 30 and 120 min after initiation of a euglycemic hyperinsulinemic clamp (3 mU x [min.sup.-1] x [kg.sup.-1]). At baseline, ZDF and ZDF-Q rats were hyperglycemic and hyperinsulinemic vs. controls. Glucose utilization in ZDF rats was 60-70% lower (P < 0.05) than in controls after 30 and 120 rain of hyperinsulinemia. In ZDF-Q rats, glucose utilization was impaired at 30 min but similar to controls at 120 rain. Basal CBV was lower in ZDF and ZDF-Q rats compared with controls (13 [+ or -] 4, 7 [+ or -] 3, and 9 [+ or -] 2 U, respectively). With hyperinsulinemia, CBV increased by about twofold in control animals at 30 and 120 min, did not change in ZDF animals, and increased in ZDF-Q animals only at 120 rain to a level similar to controls. Anatomic capillary density on immunohistology was not different between groups. We conclude that insulin-mediated capillary recruitment in skeletal muscle, which participates in glucose utilization, is impaired in animals with DM and can be partially reversed by 1 chronic ACE-I therapy. contrast ultrasound; microbubbles; blood flow; blood volume

Angiotensin-converting enzyme (ACE) inhibitors represent the front-line pharmacological treatment of heart failure, which is characterized by left ventricular (LV) dilatation and inappropriate hypertrophy. The mechanism of action of ACE inhibitors is still unclear, but evidence suggests that they may act by influencing matrix metalloproteinase (MMP) activity. This study sought to determine whether ACE inhibitors can directly regulate MMP activity and whether this results in positive structural and functional adaptations to the heart. To this end, MMP-2 activity in LV tissue extracted from rats with an aortocaval (AV) fistula was assessed by in vitro incubation as well as in vivo treatment with captopril, lisinopril, or quinapril. Furthermore, LV size and function were determined in untreated AV fistula rats, AV fistula rats treated with lisinopril (3, 5, and 8 wk), and age-matched sham-operated controls. In vitro incubation with captopril, lisinopril, or quinapril significantly reduced MMP-2 activity, as did in vivo treatment. This occurred without a reduction in the available pool of MMP-2 protein. Long-term in vivo administration of lisinopril also prevented LV dilatation, attenuated myocardial hypertrophy, and prevented changes in myocardial compliance and contractility. The results herein demonstrate that ACE inhibitors prevent MMP-2 activity and, in so doing, represent a mechanism responsible for preventing the negative structural and functional changes that occur in the rat AV fistula model of heart failure. ventricular function; ventricular dilatation; aortocaval fistula; remodeling; matrix metalloproteinase inhibition doi: 10.1152/ajpheart.00447.2006.

Time-sequential responses to endothelium-dependent and -independent vasodilators and angiotensin-converting enzyme (ACE) inhibitors were studied in the subendocardial arterioles (Endo) of canine renovascular hypertension (HT) compared with subepicardial arterioles (Epi; both < 120 [micro]m) by charge-coupled device intravital microscope. Vascular responses to acetylcholine, papaverine, and cilazaprilat were compared between normotensive (NT) and HT dogs [4 wk and 12 wk of HT (4wHT and 12wHT)]. The acetylcholine-induced vasodilation of Endo in both 4wHT and 12wHT was smaller than that of NT (both P < 0.01 vs. 4wHT and 12wHT), and that of Epi was smaller than that of NT only in 12wHT (P < 0.05). The papaverine-induced vasodilation of Endo, but not Epi, was impaired only in 12wHT (both P < 0.01 vs. NT and 4wHT). Vasodilation by cilazaprilat remained unchanged at 4wHT and 12wHT in both Epi and Endo. In conclusion, at the early stage, the endothelium-dependent response of Endo was impaired, whereas at the later stage, the endothelium-dependent and -independent responses of Endo and the endothelium-dependent response of Epi were impaired. However, the vasodilatory responses to the ACE inhibitor were maintained in both Endo and Epi of HT. endothelium-dependent and -independent vasodilators; angiotensin-converting enzyme inhibitor

Because across-the-board data indicate that renin and cyclooxygenase-2 (COX-2) expression in the kidney cortex are regulated in parallel and because ANG II can inhibit COX-2 expression, the purpose of our study was to characterize a potential general inhibitory feedback of the renin-angiotensin system on renocortical COX-2 expression in vivo. Rats were fed a high-, normal-, or low-salt diet or were chronically infused with furosemide (60 mg*[kg.sup.-1]* [day.sup.-1]) or the left renal artery was clipped, and the animals were treated in addition to or without the angiotensin-converting enzyme inhibitor ramipril (10 mg*kg.sup.-1]*[day.sup.-1]). A high-salt diet reduced expression of COX-2, whereas a low-salt diet, furosemide infusion, and renal artery stenosis stimulated COX-2 expression. Additional angiotensin-converting enzyme inhibition led to further increases in renocortical COX-2 expression by 62, 136, 300, 50, and 70% for a high-, normal-, and low-salt diet, furosemide infusion, and renal artery stenosis, respectively. Thus our data suggest a general inhibitory effect of the renin-angiotensin system on renocortical COX-2 expression. renin; angiotensin-converting enzyme inhibition; renal cortex; prostaglandins

Unilateral ureteral obstruction (UUO) is a well-established model for the study of interstitial fibrosis in the kidney. It has been shown that the reninangiotensin system plays a central role in the progression of interstitial fibrosis. Recent studies indicate that endothelin, a powerful vasoconstrictive peptide, may play an important role in some types of renal disease. To investigate the effects of angiotensin II on endothelin and its receptors in the kidney, mice were subjected to UUO and treated with or without enalapril, an orally active angiotensin-converting enzyme inhibitor, in their drinking water (100 mg/1). The animals were killed 5 days later. Using RT coupled with PCR, we measured the levels of endothelin-1, endothelin A, and endothelin B (E[T.sub.B]) along with transforming growth factor-[beta], TNF-[alpha], and collagen type IV mRNA expression in the kidney with UUO and the contralateral kidney along with interstitial expansion in the kidney cortex by a standard point counting method. We found that enalapril administration ameliorated the increased expression of ET-1 mRNA in the obstructed kidney by 44% (P < 0.02). Although the level of endothelin A mRNA expression was significantly increased in the obstructed kidney, it was not affected by enalapril. We found that enalapril treatment increased E[T.sub.B] mRNA expression by 115% (P < 0.05) and protein expression (measured by Western blot) in the kidney with an obstructed ureter. Enalapril treatment alone inhibited the expansion of interstitial volume due to UUO by 52%. Cotreatment with enalapril and the E[T.sub.B] receptor antagonist BQ-788 inhibited the expression of interstitial volume by only 19%. This study confirms that enalapril inhibits the interstitial fibrosis in UUO kidneys. It also suggests a beneficial and unforeseen effect of enalapril on the obstructed kidney by potentially stimulating the production of nitric oxide through an increased expression of the E[T.sub.B] receptor. nitric oxide formation; fibrosis; enalapril; angiotensin-converting enzyme; endothelin B receptor

It is well known that nonselective, nonsteroidal anti-inflammatory drugs inhibit renal renin production. Our previous studies indicated that angiotensin-converting enzyme inhibitor (ACEI)-mediated renin increases were absent in rats treated with a cyclooxygenase (COX)-2-selective inhibitor and in COX-2 -/- mice. The current study examined further whether COX-1 is also involved in mediating ACEI-induced renin production. Because renin increases are mediated by cAMP, we also examined whether increased renin is mediated by the prostaglandin [E.sub.2] receptor E[P.sub.2] subtype, which is coupled to [G.sub.s] and increases cAMP. Therefore, we investigated if genetic deletion of COX-1 or E[P.sub.2] prevents increased ACEI-induced renin expression. Age- and gender-matched wild-type (+/+) and homozygous null mice (-/-) were administered captopril for 7 days, and plasma and renal renin levels and renal renin mRNA expression were measured. There were no significant differences in the basal level of renal renin activity from plasma or renal tissue in COX-1 +/+ and -/- mice. Captopril administration increased renin equally [plasma renin activity (PRA): +/+ 9.3 [+ or -] 2.2 vs. 50.1 [+ or -] 10.9; -/- 13.7 [+ or -] 1.5 vs. 43.9 [+ or -] 6.6 ng ANG I * [ml.sup.-1] * [h.sup.-1]; renal renin concentration: +/+ 11.8 [+ or -] 1.7 vs. 35.3 [+ or -] 3.9; -/- 13.0 [+ or -] 3.0 vs. 27.8 [+ or -] 2.7 ng ANG I * mg [protein.sup.-1] * [h.sup.-1]; n = 6; P < 0.05 with or without captopril]. ACEI also increased renin mRNA expression (+/+ 2.4 [+ or -] 0.2; -/- 2.1 [+ or -] 0.2 fold control; n = 6-10; P < 0.05). Captopril led to similar increases in E[P.sub.2] -/- compared with +/+. The COX-2 inhibitor SC-58236 blocked ACEI-induced elevation in renal renin concentration in E[P.sub.2] null mice (+/+ 24.7 [+ or -] 1.7 vs. 9.8 [+ or -] 0.4; -/- 21.1 [+ or -] 3.2 vs. 9.3 [+ or -] 0.4 ng ANG I * mg [protein.sup.-1] * [h.sup.-1]; n = 5) as well as in COX-1 -/- mice (SC-58236-treated PRA: +/+ 7.3 [+ or -] 0.6; -/- 8.0 [+ or -] 0.9 ng ANG I * [ml.sup.-1] * [h.sup.-1]; renal renin: +/+ 9.1 [+ or -] 0.9; -/- 9.6 [+ or -] 0.5 ng ANG I * mg [protein.sup.-1] * [h.sup.-1]; n = 6-7; P < 0.05 compared with no treatment). Immunohistochemical analysis of renin expression confirmed the above results. This study provides definitive evidence that metabolites of COX-2 rather than COX-1 mediate ACEI-induced renin increases. The persistent response in E[P.sub.2] nulls suggests involvement of prostaglandin [E.sub.2] receptor subtype 4 and/or prostacyclin receptor (IP). angiotensin-converting enzyme inhibitor; cyclooxygenase-2 -/-; prostaglandin [E.sub.2] receptor subtype 2

We used spontaneously hypertensive rats to study remodeling of cardiac bioenergetics associated with changes in blood pressure. Blood pressure was manipulated with aggressive antihypertensive treatment combining low dietary salt and the angiotensin-converting enzyme inhibitor enalapril. Successive cycles of 2 wk on, 2 wk off treatment led to rapid, reversible changes in left ventricular (LV) mass (30% change in hypertension; mitochondria; mitochondrial deoxyribonucleic acid; angiotensin-converting enzyme inhibitor; spontaneously hypertensive rats; cytochrome oxidase; oxidative stress

Intrarenal A[T.sub.1] receptor and ACE binding in ANG II-induced hypertensive rats. Am J Physiol Renal Physiol 281: F19-F25, 2002.. First published August 9, 2001, 10.1152/ajprenal. 00335.2001.--The intrarenal expression of angiotensin II (ANG II) type 1 (A[T.sub.1]) receptors and angiotensin-converting enzyme (ACE) was determined in ANG II-induced hypertensive rats (80 ng/min; 2 wk). Systolic blood pressure averaged 184 [+ or -] 3 and 125 [+ or -] 1 mmHg in ANG II-infused compared with Sham rats on day 12. Total kidney A[T.sub.1] receptor protein levels were not altered significantly. A[T.sub.1] receptor binding mapped by quantitative in vitro autoradiography was significantly decreased in glomeruli (172 [+ or -] 25 vs. 275 [+ or -] 34 disintegrations * [min.sup.-1] * [mm.sup.-2]) and the inner stripe of the outer medulla (121 [+ or -] 17 vs. 178 [+ or -] 19 disintegrations * [min.sup.-1] * [mm.sup.-2]), but not proximal convoluted tubules (48 [+ or -] 9 vs. 58 [+ or -] 6 disintegrations * [min.sup.-1] * [mm.sup.-2]) of ANG II-infused compared with Sham rats. Proximal tubule ACE binding was significantly augmented (132 [+ or -] 4 vs. 97 [+ or -] 3 disintegrations * [min.sup.-1] * [mm.sup.-2]) in ANG II-infused rats. In summary, during ANG II-induced hypertension, glomeruli and inner stripe of the outer medulla have reduced A[T.sub.1] receptor binding. Proximal convoluted tubules exhibit maintained A[T.sub.1] receptor density and increased ACE binding, which together with the elevated ANG II levels suggest that ANG II exerts a sustained influence on tubular reabsorption and consequently contributes to the development and maintenance of ANG II-dependent hypertension. Western blot analysis; glomeruli; proximal convoluted tubules; outer medulla; in vitro autoradiography; osmotic minipump

Research demonstrates production of fermented milks containing angiotensin-I-converting-enzyme-inhibitory peptides by two species of Lactobacillus species. Data on ACE-inhibitory peptide sequences, chemical synthesis, and biological activity are presented.

Early long-term therapy with the AT(sub 1)-receptor blocker valsartan decreases preload and afterload for dogs with moderate heart failure, but has few benefits in attenuating the progression of left ventricular dysfunction and chamber remodeling. This was concluded in a study that sought to determine the effects of early long-term monotherapy with the angiotensin II AT(sub 1)-receptor antagonist valsartan on the progression of left ventricular dysfunction and remodeling in dogs with moderate heart failure. Treatment with valsartan substantially reduced mean aortic pressure and left ventricular end-diastolic pressure compared with control.

The two-stage model described by Johnson and Schoemaker is used in measuring changes in angiotensin II (ANG II) in the left ventricle versus plasma of live rats after acute coronary ligation. The role of renal renin on changes in ANG II after myocardial infarction by bilateral nephrectomy has also been examined. The effects of angiotensin-converting enzyme inhibitors with low enalapril versus high quinapril affinity on early changes in cardiac and plasma ANG II has also been studied. Experimental results indicated a rapid but short-lived increase in cardiac tissue angiotensin II which does not depend on renal renin.

The roles of the renin-angiotensin and the kinin-kallikrein systems in endothelial degradation were examined during the early stages of hypertension in rats. A one-kidney, one-clip model (1K, 1C) was utilized to characterize the effect of the angiotensin II type 1A receptor antagonist Losartan and the bradykinin B2 receptor on endothelial function, the determiner of vascular relaxation or constriction. However, endothelial dysfunctions identified were reversed following treatment with angiotensin converting enzyme inhibitor or angiotensin II type 1A receptor antagonist.

Bradykinin appears to be involved in the action of ACE inhibitors, which are used to lower blood pressure in people with hypertension. Bradykinin is a naturally occurring chemical in the body that dilates blood vessels. Researchers measured blood pressure in 20 healthy people and seven people with hypertension after they took an ACE inhibitor. The measurement was repeated after they took a drug that blocks bradykinin in addition to the ACE inhibitor. The drop in blood pressure was less when the volunteers took the bradykinin inhibitor and the ACE inhibitor.

The consequences of blocking the renin-angiotensin system on sympathetic baroreflex using the ANG II receptor antagonist losartan was examined and its effects were compared to the angiotensin-converting enzyme inhibitor enalaprilat. Findings show that losartan has a significant excitatory effect on the central pathways influencing the renal sympathetic nerve activity (RSNA) which results in an increase in the upper plateau and range of the RSNA baroreflex curve. Moreover, a similar effect was also observed in enalaprilat but only during hypoxic conditions.

A study was conducted to test the hypothesis that nitric oxide and/or prostacyclin block hypertrophy of adult rat ventricular cardiomyocytes induced by angiotensin II in vitro. The study demonstrates that the antihypertrophic effects of bradykinin in vitro are critically dependent on the release of nitric oxide from endothelial cells. Prostacyclin or another cyclooxygenase product may possibly also play an antihypertrophic effect.

The effects of neonatal administration on the ability of the rat kidneys to secrete acid and acidify urine were investigated using metabolic balance studies and clearance experiments in anesthetized adult rats which received enalapril from day 5 to 24. Results reveal that the kidney tubules of these rats have impaired urinary concentrating function but intact acid excretion and urinary acidification functions.

Young spontaneously hypertensive rats (SHR) at the start of significant hypertension were observed to have an increased expression of type 1 angiotensin II receptor (AT1R) mRNA and immunoreacive protein compared to age-matched Wistar-Kyoto rats. On the other hand, there were no differences in AT1R in the adult SHR. The increased expression in young SHR was prevented either by angiotension converting enzyme inhibition or exogenous administration of dopamine precursor.

Researchers have tested the belief that the persistent antihypertensive effect of long-term angiotensin-converting enzyme inhibitor treatment in spontaneously hypertensive rats (SHR) a long time after treatment has ceased is associated with a shift in the pressure-natriuresis relation. Attention was also given to the mechanism of resetting of pressure natriuresis after long-term angiotensin I-converting enzyme (ACE) inhibition in SHR. It was established that ACE inhibitors have specific actions on vascular structure, producing significant long-term effects on renal function.

The direct and flow-mediated effects of bradykinin on coronary and regional myocardial function were analyzed in conscious dogs chronically-instrumented with left ventricular micromanometers and circumflex coronary catheter. Analysis of the effects of bradykinin in chronically instrumented dogs indicated the role of the coronary vasodilator as an endogenous cardioprotective agent that does not modify regional myocardial function. Furthermore, coronary blood supply was elevated by the potentiation of bradykinin with angiotensin-converting enzyme inhibitors.

The effects of physiological elevations in arginine vasopressin (AVP) plasma levels on sympathetic activity and baroreflex function was analyzed in human subjects. Analysis of plasma AVP elevations in normal human subjects after the administration of angiotensin-converting enzyme inhibitors indicated the presence of normal baseline sympathetic nervous system activity based on plasma norepinephrine (NE) levels and plasma NE spillover. Furthermore, the responses of heart rate, forearm vascular resistance and systemic NE spillover to baroreceptor unloading was not affected by elevated AVP in normal human subjects.

Normotensive and renovascular hypertensive dogs were analyzed to determine the role of the renin-angiotensin systems (RAS) in the regulation of the mechanical properties of the aortic wall. The viscosity index was reduced and the compliance-pressure curve was shifted upwards by the administration of E-3174 losartan metabolite and enalaprilat in hypertensive dogs. However, administration of E-3174 in normotensive dogs did not alter the compliance-pressure curve and viscosity index indicating the role of angiotensin converting enzymes in modifying arterial viscoelastic parameters.

The brain, heart, kidney and erythrocytes of mice treated with angiotensin converting enzyme inhibitors (ACEi) were analyzed to determine the effects of ACEi on tissue antioxidant defenses. Analysis of mucine kidney medulla, heart and erythrocytes after pretreatment with enalapril or captopril indicated the presence of elevated CuZn-superoxide dismutase (SOD) activity. The mucine tissues also exhibited enhanced nonenzymatic antioxidant capacity due to ACEi-induced synthesis of antioxidants.

Spontaneously hypertensive rats (SHR) were analyzed to determine the effects of short-term arginine vasopressin (AVP) receptor antagonists and angiotensin-converting enzyme (ACE) blockade on hypertension. Analysis of the developmental phase of hypertension in SHRs after the inhibition of V1A AVP receptors and ACE blockade indicated the presence of inhibited genetic expression of hypertension. The effects of V1A inhibition and ACE blockade indicated the role of AVP receptors and angiotensin II in the pathogenesis of genetic hypertension.

The effects of angiotensin-converting enzyme (ACE) inhibitors such as captopril and imidaprilat during low-renin hypertension were analyzed in conscious deoxycorticosterone acetate (DOCA) salt hypertensive dogs. Administration of captopril and imidaprilat on conscious DOCA salt hypertensive dogs increased urine flow rate and reduced mean arterial pressure. The significant hypotensive and renal effects of the ACE inhibitors were due to the action of bradykinin and prostaglandin formation which was mediated by angiotensin II synthesis in the kidney.

The kinetic parameters of bradykinin (BK) and [des-Arg9]BK in the serum of species with or without enalaprilat after in vitro incubation was analyzed to determine interspecies metabolic differences. Significant interspecies differences were detected in the half-life of bradykinin and [des-Arg9]BK of the serum samples. The serum samples from several animal species also exhibited different metabolic pathways for plasma kininase I and angiotensin I-converting enzyme.

Chronic heart failure leads to progressive endothelium dysfunction and thus impairs vasodilator response to acetylcholine in peripheral resistance arteries. However, vascular structure and media collagen content are unaffected. Chronic treatment with angiotensin-converting enzyme inhibitor perindopril improves responses to acetylcholine after 30 and 365 days of treatment. Vascular structure improves only after 365 days. Thus, angiotensin-converting enzyme inhibitors have useful effects on hemodynamics and survival during chronic heart failure.

The effects of angiotensin-converting enzyme (ACE) inhibitors on sodium-potassium (Na+-K+) pumping are related to the effects of angiotensin II (ANG II) metabolism. Treatment of rabbit myocytes with ANG II type I receptor antagonist losartan increased Na+-K+ pump current. Myocytes showed a similar increase after treatment with ACE inhibitors. Furthermore, myocytes from controls and from those treated with ANG II exhibited reductions in Na+-K+ pump current.

Examination of the effects of the treatment with an angiotensin-converting enzyme (ACE) inhibitor cilazapril on left ventricular function under controlled loading conditions in spontaneously hypertensive rats (SHR) reveals that the ACE inhibitor decreases left ventricular contractility. Treatment with cilazapril inhibits heart performance in SHR hearts but exerts no influence in the Sprague-Dawley group. Impairment of pump function in SHR hearts due to cilazapril treatment accompanies a decreased velocity of shortening of papillary muscles.

Enalaprilat is an angiotensin-converting enzyme inhibitor that exerts a potent hemo-dynamic effect by increasing hepatic vascular capacitance during ischemic heart failure. The increased capacitance occurs due to active changes in vascular smooth muscle tone. Enalaprilat increases hepatic vascular volume without affecting splenic volume.

Studies of various models of hypertension do not reveal different hypertensive and natriuretic responses with mixed inhibitor RB105 at 25mg per kg. The natriuretic response may be linked to neutral endopeptidase (NEP) inhibition. In acetate-induced hypertensive rats the hypotensive effect is caused by NEP inhibition. In renovascular hypertensive rats the inhibition of Angiotensin-converting enzyme leads to hypotensive effects.

Study of normotensive male Wistar/Rij rats indicates that some age-related changes include fixed systemic blood pressure, enhanced intrarenal vascular resistance and a corresponding step-wise reduction in renal blood flow and glomerular filtration rate per kidney weight. The morphological changes that occur include glomerular hypertrophy, glomerular basement thickening and reduced capillary surface.

The effect of chronic intake of Benazepril, an angiotensin converting enzyme, on heart and renal functions in the early stagesof heart failure was investigated in dogs. Chronic administration of Benazeprilled to the elevation of cardiac output and the reduction of total peripheral vascular resistance. Further the rate of sodium and water balance increases wassignificantly less in dogs receoving Benazapril compared to controls. No significant differences in other kidney functions were demonstrated. Administration of Benazepril in control dogs in later stages was not as effective compared with chronic administration.