Angioedema associated with angiotensin II receptor antagonist losartan

Angioedema has not been associated with losartan therapy in hemodialysis patients, as it has been with angiotensin converting enzyme (ACE) inhibitors. We report the case of a hemodialysis patient who previously had angioedema after therapy with ACE inhibitors and again had angioedema while taking losartan. We suggest caution in using losartan in patients with known sensitivity to ACE inhibitors manifested by angioedema.     

Uricosuric effect of the angiotensin II receptor antagonist losartan in heart transplant recipients

BACKGROUND: The angiotensin II receptor antagonist losartan is an effective antihypertensive agent with unique uricosuric properties. This study evaluates the uricosuric effects of losartan in 10 hypertensive heart transplant patients with hyperuricemia. METHODS: The patients were randomized to receive losartan 50 mg once daily and enalapril 20 mg once daily for 4 weeks according to a double-blind crossover design. Office blood pressure, plasma uric acid levels, and urinary uric acid excretion were monitored throughout the study. RESULTS: Plasma uric acid levels decreased significantly after 4 weeks of treatment with losartan (P<0.05) but not with enalapril. On day 1 and after 1 month of treatment, a significant increase in uric acid excretion was observed only with losartan. Significant decreases in office systolic and diastolic blood pressures were obtained with enalapril but not with losartan. CONCLUSIONS: Losartan effectively lowers plasma uric acid levels in hyperuricemic heart transplant patients.     

The effect of acarbose on insulin sensitivity in subjects with impaired glucose tolerance

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on postprandial plasma glucose and insulin and insulin sensitivity in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Subjects with IGT were randomly treated in a double-blind fashion with placebo (n = 10) or acarbose (n = 8) at 100 mg t.i.d. for 4 months. All subjects were submitted before randomization and at the end of the study to a standardized breakfast and a 12-h daytime plasma glucose and plasma insulin profile, and insulin sensitivity was measured as steady-state plasma glucose (SSPG) using the insulin suppression test. RESULTS: While placebo had no effect on postprandial plasma glucose and plasma insulin incremental area under the curve (AUC) (3.03 +/- 0.5 vs. 3.76 +/- 0.6 mmol.h-1.l-1, P = NS; 1,488 +/- 229 vs. 1,609 +/- 253 pmol.h-1.l-1, P = NS), acarbose resulted in a significant reduction for both glucose (1.44 +/- 0.3 vs. 4.45 +/- 0.9 mmol.h-1.l-1, P = 0.002) and insulin (626.7 +/- 104.3 vs. 1,338.3 +/- 220.5 pmol.h-1.l-1, P = 0.003). The reduction in 12-h plasma glucose and insulin AUC on acarbose (11.2 +/- 2.1 mmol.h-1.l-1 and 7.5 +/- 0.7 nmol.h-1.l-1) was significantly greater than that on placebo (4.0 +/- 1.6 mmol.h-1.l-1 and 0.8 +/- 0.4 nmol.h-1.l-1) (P = 0.014 and 0.041). While SSPG was not affected by placebo (13.9 +/- 0.4 vs. 13.8 +/- 0.3 mmol/l; P = NS), it was significantly improved by acarbose (10.9 +/- 1.4 vs. 13.1 +/- 1.5 mmol/l, P < 0.004) and was also significantly different from placebo at 4 months (P < 0.02). CONCLUSIONS: It is concluded that in subjects with IGT, acarbose treatment decreases postprandial plasma glucose and insulin and improves insulin sensitivity. Acarbose may therefore be potentially useful to prevent the progression of IGT to NIDDM.     

Effect of losartan, an angiotensin II receptor antagonist, on portal pressure in cirrhosis

Administration of angiotensin II causes an increase in portal pressure, and plasma concentration of angiotensin II is elevated in patients with cirrhosis, suggesting that angiotensin II may be involved in the pathogenesis of portal hypertension in cirrhosis. We evaluated the effect of the orally active angiotensin II receptor antagonist, losartan, on portal pressure in patients with cirrhosis and portal hypertension. Thirty patients with severe (hepatic venous pressure gradient [HVPG] >/= 20 mm Hg) and 15 patients with moderate (HVPG < 20 mm Hg) portal hypertension at baseline measurement were treated with an oral dose of 25 mg losartan once daily for 1 week and compared with 15 (HVPG >/= 20 mm Hg) and 10 (HVPG < 20 mm Hg), respectively, cirrhotic controls. On the seventh day, HVPG was determined again, and blood pressure, heart rate, body weight, and parameters of liver and kidney function were recorded. Losartan induced a significant (P <.001) decrease of HVPG in the patients with severe (-46.8% +/- 15.5%) and moderate (-44.1% +/- 14.7%) portal hypertension, while no significant change was seen in the controls. Losartan caused a slight but significant (P <.01) fall in mean arterial blood pressure (-3.1 +/- 5.0 and -3.5 +/- 4.3 mm Hg, respectively). One patient treated with losartan had a short symptomatic hypotensive reaction after the first dose of losartan that did not recur despite continued treatment. No deterioration of liver or kidney function was observed. The present study indicates that angiotensin II blockade with orally administered losartan is safe and highly effective in the treatment of portal hypertension.     

Anti-atherosclerotic action of angiotensin converting enzyme II. Effect on metabolism of kinin, free radical reaction, sensitivity to insulin and lipid metabolism

Blockade of the renin-angiotensin system reduces the development of the atherosclerotic process after vascular injury and in hyperlipidemic animals. ACE-inhibitors inhibit vascular smooth muscle cells migration and proliferation, macrophage-foam cell accumulation and preserve the antiaggregatory and antithrombotic function of the endothelium in atherosclerotic vessels. In addition to the inhibition of angiotensin II synthesis, reduced degradation of kinins and improvement of insulin action after ACE-inhibition may be responsible for observed actions. ACE-inhibitors may have also influence on lipids metabolism, including low density lipoprotein oxidation. Despite this, ACE-inhibitors failed to prevent restenosis after coronary angioplasty in humans. One reason for the lack of ACE-inhibitors effect in human restenosis might depend on the activation of the alternative angiotensin II-generating system in human arteries after vascular injury.     

Effects of angiotensin II-receptor blockade with losartan on insulin sensitivity, lipid profile, and endothelin in normotensive offspring of hypertensive parents

BACKGROUND: Acute liver failure (ALF) secondary to malignant infiltration of the liver is rare and is diagnosed often only after death. AIMS: To determine diagnostic factors and particular clinical patterns of illness. METHODS: Review of case notes from all patients with ALF secondary to hepatic infiltration admitted to this unit over an 18 year period (1978-1995). RESULTS: From a total of 4020 admissions, 18 patients were identified with ALF attributable to hepatic infiltration. Mean age was 40.7 years. Aetiology was non-Hodgkin's lymphoma in nine patients, Hodgkin's disease in three, infiltrative metastatic carcinoma in four, and haemophagocytosis with no precipitant cause in two cases. Prodromal symptoms were non-specific, but occurred at least two to four weeks before onset of ALF, making the presence of such symptoms of value in differential diagnosis of the cause of ALF. Clinical examination and investigations were unhelpful in distinguishing these cases from more usual causes of ALF. Usually, the clinical course was of rapid deterioration and death from multiorgan failure, and only one patient survived. Diagnosis was made during life in 15 patients. Histology showed evidence of widespread hepatocellular necrosis, with diffuse infiltration by tumour cells rather than focal cellular aggregation. CONCLUSIONS: Only with accurate histological diagnosis from liver biopsy and institution of specific therapy early in the management of such patients will the best chance of recovery be achieved. In every case of ALF with prodromal symptoms or abnormal imaging, hepatic histology should be obtained by liver biopsy as soon as possible to diagnose infiltrative hepatic disease.     

Effect of losartan, an angiotensin II receptor antagonist, on response of cortisol and aldosterone to adrenocorticotrophic hormone

Many imidazole derivatives are shown to inhibit adrenal steroid biosynthesis. The present study was undertaken to examine an effect of another imidazole derivative, losartan (an angiotensin II receptor antagonist), on responses of cortisol and aldosterone to adrenocorticotrophic hormone (ACTH). Nine patients with essential hypertension were given placebo orally for 7 days and 50 mg of losartan for the next 9 days. Response of serum cortisol and plasma aldosterone to intramuscular ACTH injection were determined before and at the end of the treatment with losartan. Serum cortisol and plasma aldosterone significantly increased after ACTH injection in both periods of treatment (placebo and losartan). The increments in these parameters during treatment with losartan were not significantly different from those during treatment with placebo. These results suggest that the inhibitory effect of losartan on adrenal steroid biosynthesis is negligible.     

ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients

The aim of this study was to compare the effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin II antagonist losartan on insulin sensitivity and plasma fibrinogen in overweight hypertensive patients. Twenty-eight overweight mild to moderate [diastolic blood pressure (DBP) >90 and <110 mm Hg] hypertensives aged 43-64 years, after a 4-week placebo period, were randomized to perindopril, 4 mg o.d., or losartan, 50 mg o.d., for 6 weeks. Then, after a new placebo period, patients were crossed to the alternative regimen for further 6 weeks. At the end of the placebo and of the treatment periods, blood pressure was measured, plasma fibrinogen was evaluated, and insulin sensitivity was assessed by the euglycemic, hyperinsulinemic clamp technique. Glucose infusion rate (GIR) during the last 30 min of clamp and total glucose requirement (TGR) were evaluated. Both perindopril and losartan reduced SBP (by a mean of 20.2 mm Hg, p < 0.001 vs. placebo; and 15.8 mm Hg, p = 0.002 vs. placebo, respectively) and DBP (by a mean of 15.2 mm Hg, p = 0.001 vs. placebo, and 11.8 mm Hg, p = 0.01 vs. placebo respectively), with no difference between the two treatments. GIR was significantly increased by perindopril (+2.91 mg/min/kg, p = 0.042 vs. placebo), but not by losartan (+0.28 mg/min/kg, NS). TGR was not modified by losartan but was increased by perindopril (+9.3 g, p = 0.042 vs. placebo). Plasma fibrinogen levels were reduced by perindopril (-53.4 mg/dl, p = 0.022 vs. placebo) but not by losartan (-16.8 mg/dl, NS). The perindopril-induced decrease in fibrinogen was correlated with the increase in GIR (r = 0.39; p < 0.01). These findings suggest that fibrinogen decrease produced by the ACE inhibitor is related to its action on insulin sensitivity, which seems to be dependent not on angiotensin II blockade but rather on other mechanisms.     

Effects of angiotensin II and losartan in the forearm of patients with essential hypertension

OBJECTIVE: Angiotensin II type 1 receptor-mediated constrictor effects may be modulated by hypertension-related vascular changes, changes in receptor function and in neurohumoral activity. DESIGN: The forearm blood flow (FBF) effects of angiotensin II, methoxamine, and losartan were investigated in essential hypertensive patients. Minimal forearm vascular resistance was measured to determine structural vascular changes. METHODS: Seven hypertensive patients were selected, and seven matched normotensives. Angiotensin II (0.01-10 ng/kg per min) was infused during predilatation by sodium nitroprusside (6.1 +/- 0.6 ng/kg per min) before and during losartan infusion (0.3-3 microg/kg per min). Methoxamine (0.2-2 microg/kg per min) was co-infused with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine. FBF, measured by venous occlusion plethysmography, was expressed as the change in FBF ratio (FBFinfused arm/FBFnon-infused arm). RESULTS: Baseline FBF (infused arm) was increased by sodium nitroprusside from 2.56 +/- 0.80 to 5.46 +/- 0.92 (P<0.05) and from 2.66 +/- 0.25 to 5.42 +/- 0.40 ml/100 ml per min (P<0.05) in the hypertensive and normotensive group, respectively. Baseline forearm vascular resistance (FVR) was higher in the hypertensive than in the normotensive group [51 +/- 8 versus 33 +/- 3 mmHg/ (ml/100 ml per min); P<0.05]. Angiotensin II caused a maximal change in FBF ratio (Emax) by -70 +/- 3 and -72 +/- 6% in the hypertensive and normotensive group, respectively (NS). Tachyphylaxis did not occur. Infusions of losartan at 0.3, 1 and 3 microg/kg per min reduced the Emax values from -70 +/- 3 to -50 +/- 5, -45 +/- 5 and -15 +/- 2%, respectively, in the hypertensive group, and from -72 +/- 6 to -62 +/- 4, -45 +/- 2 and -32 +/- 2%, respectively, in the normotensive group (NS). Infusion of methoxamine significantly reduced the FBF ratio by -58 +/- 6 and -69 +/- 5% in the hypertensive and normotensive groups, respectively (NS). Minimal FVR, after forearm ischemia, was the same in hypertensives and normotensives, namely 3.2 +/- 0.7 and 3.2 +/- 0.4 mmHg/(ml per 100 ml per min), respectively (NS). CONCLUSIONS: Angiotensin II type 1- and alpha1-mediated vascular effects were unchanged by essential hypertension. Baseline FVR was greater in the hypertensives than in the normotensives, while minimal FVR was the same. These results indicate that the forearm vascular bed of the patient group studied does not show important structural and renin-angiotensin system-related functional changes as a result of hypertension.     

Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients

We investigated the effects of angiotensin II (Ang II) type 1 receptor blockade with losartan on the renin-angiotensin-aldosterone system in hypertensive patients (supine diastolic blood pressure, 95 to 110 mm Hg). Qualifying patients (n = 51) were allocated to placebo, 25 or 100 mg losartan, or 20 mg enalapril. Blood pressure, plasma drug concentrations, and renin-angiotensin-aldosterone system mediators were measured on 4 inpatient days: end of placebo run-in, after first dose, and 2 and 6 weeks of treatment. Plasma drug concentrations were similar after the first and last doses of losartan. At 6 weeks, 100 mg losartan and 20 mg enalapril showed comparable antihypertensive activity. Four hours after dosing, compared with the run-in day, 100 mg losartan increased plasma renin activity 1.7-fold and Ang II 2.5-fold, whereas enalapril increased plasma renin activity 2.8-fold and decreased Ang II 77%. Both drugs decreased plasma aldosterone concentration. For losartan, plasma renin activity and Ang II increases were greater at 2 than at 6 weeks. Effects of losartan were dose related. After the last dose of losartan, plasma renin activity and Ang II changes were similar to placebo changes by 36 hours. These results indicate that long-term blockade of the feedback Ang II receptor in hypertensive patients produces modest increases of plasma renin activity and Ang II that do not appear to affect the antihypertensive response to the antagonist.     

The effect of central angiotensin II receptor blockade on interleukin-1beta- and prostaglandin E-induced fevers in rats: possible involvement of brain angiotensin II receptor in fever induction

We investigated the role of the brain angiotensin II (Ang II) receptor subtypes AT1 and AT2 in the development of fever induced in freely moving rats by administration of interleukin-1beta (IL-1beta) or prostaglandin E2 (PGE2). Intraperitoneal (i.p.) injection of IL-1beta (2 microg/kg) induced a marked fever of rapid onset. Intracerebroventricular (i.c.v.) administration, immediately before IL-1beta injection, of a selective AT2 receptor antagonist, CGP42112A (5 or 20 microg), reduced the fever in a dose-related manner. Rats given an i.c.v. injection of PGE2 (200 ng) developed a monophasic fever response that was attenuated by i.c.v. treatment with CGP42112A (10 or 20 microg) in a dose-related manner. The IL-1beta (2 microg/kg i.p.)- and PGE2 (200 ng i.c.v.)-induced fevers were unchanged by the selective AT1 receptor antagonist losartan (60 microg i.c.v.). Treatment with exogenous Ang II (100 ng i.c.v.), which itself had no effect on resting body temperature, resulted in an enhancement of the PGE2 (50 ng i.c.v.)-induced fever. The administration of CGP42112A (2 and 5 microg) into the rostral hypothalamus (preoptic/anterior hypothalamic region) reduced fevers induced by IL-1beta (2 microg/kg i.p.) or intrahypothalamic (i.h.) PGE2 (100 ng). Moreover, i.h. injection of Ang II (25 ng) augmented the PGE2 (25 ng i.h.)-induced fever. Finally, the i.h. administration, 15 min before i.h. PGE2 (100 ng), of the angiotensin-converting enzyme (ACE) inhibitor lisinopril (5 and 10 microg) attenuated the PGE2-induced fever. These results suggest that brain AT2 receptors contribute to the induction of such febrile responses in rats.     

Trp64Arg mutation of beta 3-adrenergic receptor and insulin sensitivity in subjects with glucose intolerance

We investigated the relationship between the Trp64Arg mutation in the beta 3-adrenergic receptor gene and insulin sensitivity, which was evaluated by the euglycemic-hyperinsulinemic-clamp technique, in 54 patients with impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM) who were not receiving insulin therapy. The frequencies of Trp/Trp, Trp/Arg, and Arg/Arg genotypes in the patients were 63.0, 33.3, and 3.7%, respectively, which did not differ significantly from those of the 227 controls (67.0, 33.3, and 3.7%, respectively, which did not differ significantly from those of the 227 controls (67.0, 31.3, and 1.8%, respectively). The mean glucose infusion rate of the 34 patients with Trp/Trp did not differ from that of the 18 patients with Trp/Arg (4.3 +/- 2.2 and 5.3 +/- 2.4 mg/kg/min, respectively); while that of the 2 patients with Arg/Arg was 11.5 mg/kg/min. There were no differences in the BMI or fat distribution in the abdomen between each genotype of patients, although the frequency of the Arg64 allele tended to increase with body mass index (BMI) in the control subjects under 60 years of age, which suggests that the mutation is involved in weight gain.     

Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension

OBJECTIVE: To evaluate the blood pressure lowering efficacy as well as tolerability and safety of the angiotensin II antagonist losartan compared with that of the angiotensin converting enzyme inhibitor enalapril in patients with mild-to-moderate essential hypertension. DESIGN AND METHODS: The study was a multicentre, double-blind, double-dummy, randomized, parallel study. Patients (n = 407) with diastolic blood pressure > or = 95 and < or = 120 mmHg at the end of a 2-week baseline placebo period were randomly allocated to receive either 50 mg losartan once a day or 20 mg enalapril once a day for 12 weeks. Blood pressure, clinical and laboratory safety, specific symptoms including coughing determined using a symptoms questionnaire and metabolic variables were examined at baseline and at weeks 6 and 12. RESULTS: Both losartan and enalapril decreased systolic and diastolic blood pressure from baseline at weeks 6 and 12. Blood pressure changes from baseline at trough (22-26 h after the dose) did not differ between the two groups in the per-protocol analysis. Response to treatment at trough was excellent or good (diastolic blood pressure < 90 mmHg or reduction in diastolic blood pressure of 10 mmHg) in 51 and 53% of the patients in the losartan and enalapril groups, respectively. Enalapril administration increased dry coughing symptoms whereas losartan did not. The incidence of dry coughing was 1.0 and 12.2% as a spontaneously reported discomfort at week 12 and 3.0 and 15.1% as a clinical adverse experience in the losartan and enalapril groups, respectively. The difference from baseline at week 12 in the incidence of dry coughing between the two groups was 14.9% as a specific symptom in the symptoms questionnaire. Losartan reduced serum uric acid concentration, whereas effects on other metabolic parameters did not differ between the groups. CONCLUSIONS: Losartan is an effective and well-tolerated antihypertensive drug showing similar blood-pressure-lowering efficacy to that of enalapril at trough. However, in contrast to enalapril, losartan does not increase the incidence of dry coughing. Thus, the angiotensin II antagonist losartan provides a promising new approach to treatment of hypertension.     

Inhibition of sympathetic outflow by the angiotensin II receptor antagonist, eprosartan, but not by losartan, valsartan or irbesartan: relationship to differences in prejunctional angiotensin II receptor blockade

It is well established that angiotensin II can enhance sympathetic nervous system function by activating prejunctional angiotensin II type I (AT1) receptors located on sympathetic nerve terminals. Stimulation of these receptors enhances stimulus-evoked norepinephrine release, leading to increased activation of vascular alpha 1-adrenoceptors and consequently to enhanced vasoconstriction. In the present study, the effects of several chemically distinct nonpeptide angiotensin II receptor antagonists were evaluated on pressor responses evoked by activation of sympathetic outflow through spinal cord stimulation in the pithed rat. Stimulation of thoracolumbar sympathetic outflow in pithed rats produced frequency-dependent pressor responses. Infusion of sub-pressor doses of angiotensin II (40 ng/kg/min) shifted leftward the frequency-response curves for increases in blood pressure, indicating augmented sympathetic outflow. Furthermore, pressor responses resulting in spinal cord stimulation were inhibited by the peptide angiotensin II receptor antagonist, Sar1, Ile8 [angiotensin II] (10 micrograms/kg/min). These results confirm the existence of prejunctional angiotensin II receptors at the vascular neuroeffector junction that facilitate release of norepinephrine. The nonpeptide angiotensin II receptor antagonist, eprosartan (0.3 mg/kg i.v.), inhibited the pressor response induced by spinal cord stimulation in a manner similar to that observed with the peptide antagonist, Sar1, Ile8[angiotensin II]. In contrast, equivalent doses (0.3 mg/kg i.v.) of other nonpeptide angiotensin II receptor antagonists, such as losartan, valsartan, and irbesartan, had no effect on spinal cord stimulation of sympathetic outflow in the pithed rat. Although the mechanism by which eprosartan, but not the other nonpeptide angiotensin II receptor antagonists, inhibits sympathetic outflow in the pithed rat is unknown, one possibility is that eprosartan is a more effective antagonist of prejunctional angiotensin II receptors that augment neurotransmitter release. Because eprosartan is more effective in inhibiting sympathetic nervous system activity compared to other chemically distinct nonpeptide angiotensin II receptor antagonists, eprosartan may be more effective in lowering systolic blood pressure and in treating isolated systolic hypertension.     

The effect of stevioside on glucose metabolism in rat

This study was conducted to determine the effect of stevioside (SVS) on glucose metabolism. The experiments were performed in male Wistar rats treated with SVS either by intravenous infusion or feeding. SVS infusion (150 mg/mL) was carried out in doses of 0.67, 1.00, and 1.33 mL.kg-1 body weight.h-1. The plasma glucose level significantly increased both during and after SVS infusion, whereas it was not affected by SVS feeding (13.3 mL.kg-1 body weight). The glucose turnover rate (GTR) of [14C(U)]glucose and [3(-3)H]glucose was not significantly different between control and SVS infusion animals. Percent glucose carbon recycling and glucose clearance were reduced from 28.7 +/- 1.3 to 23.0 +/- 1.6% (p < 0.05) and from 6.46 +/- 0.34 to 4.99 +/- 0.20 mL.min-1.kg-1 body weight (p < 0.01), respectively. The plasma insulin level did not change, whereas the plasma glucose level significantly increased from 120.3 +/- 5.9 to 176.8 +/- 10.8 mg% (p < 0.01) during SVS infusion. Animals pretreated with angiotensin II and arginine vasopressin showed no significant effect, while animals pretreated with prazosin had an attenuated hyperglycemic effect of SVS infusion. Pretreatment with indomethacin or N omega-nitro-L-arginine methyl ester (L-NAME) alleviated the plasma glucose level during the second period of SVS infusion. Pretreatment with the combination infusion of indomethacin and L-NAME reduced the plasma glucose level from 117.0 +/- 1.8 to 109.0 +/- 1.7 mg% (p < 0.001), and normalized the plasma glucose level in the second period of SVS infusion. Insulin infusion inhibited the hyperglycemic effect of SVS infusion. The present results show that the elevation of the plasma glucose level during SVS infusion is not due to the reduction of the insulin level. It is probably the effect of SVS on glucose transport across the cell. Insulin response to a high plasma glucose level is suppressed during SVS infusion. Several interactions among norepinephrine, prostaglandin, and nitric oxide are involved in modulating the hyperglycemia during SVS infusion.     

The mechanisms of the improvement of insulin sensitivity by angiotensin converting enzyme inhibitor

To investigate the role of kinins in augmentation of insulin sensitivity by angiotensin converting enzyme inhibitor (ACEI), the effects of ACEI (delapril) on the insulin resistance in fructose-fed rats (FFR) were evaluated with or without the administration of bradykinin receptor antagonist (Hoe 140). Male Sprague-Dawley rats were fed on fructose rich chow (FFR) or standard chow (control) for 4 weeks and treated with 10 mg/kg/day of delapril with or without Hoe 140 (0.5 mg/kg/day) for an additional 2 weeks. Steady state plasma glucose (SSPG) and steady state plasma insulin (SSPI) were determined while the rats were conscious. Insulin (2.5 mU/kg/min) and glucose (8 mg/kg/min) were simultaneously infused to determine insulin sensitivity in each group. Mean blood pressure (MBP), SSPG and SSPI were significantly higher in FFR than in control, and were significantly lower in the FFR+delapril than in FFR+vehicle. There were no difference in MBP, SSPG and SSPI between FFR+delapril+vehicle and FFR+delapril+Hoe 140. We concluded that the main mechanisms of improving the insulin sensitivity by ACEI may not be the enhancement of kinins but the suppression of angiotensin II in FFR.