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Biomedical subjects

T J Allen

Publications and source records attributed to T J Allen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Endothelin receptor antagonism ameliorates mast cell infiltration, vascular hypertrophy, and epidermal growth factor expression in experimental diabetes.

Vascular hypertrophy, a feature of experimental and human diabetes, has been implicated in the pathogenesis of the microvascular and macrovascular complications of the disease. In the present study, we sought to examine the role of endogenous endothelin and its relation to vascular growth factors in the mediation of vascular hypertrophy in experimental diabetes and to examine the contribution of mast cells to this process. Vessel morphology, endothelin, growth factor gene expression, and matrix deposition were studied in the mesenteric arteries of control and streptozotocin-induced diabetic Sprague-Dawley rats treated with or without the dual endothelin(A/B) receptor antagonist bosentan (100 mg x kg(-1) x d(-1)) during a 3-week period. Compared with control animals, diabetic animals had significant increases in vessel weight, wall-to-lumen ratio, mast cell infiltration, extracellular matrix deposition, and gene expression of epidermal growth factor (EGF) and transforming growth factor-beta(1). In diabetic, but not control, vessels, not only were EGF mRNA and endothelin present in endothelial cells, but also their expression was observed in adventitial mast cells. Immunoreactive endothelin was present in the media of mesenteric vessels of diabetic, but not control, animals. Bosentan treatment significantly reduced mesenteric weight, wall-to-lumen ratio, mast cell infiltration, matrix deposition, and EGF mRNA but did not prevent the overexpression of transforming growth factor-beta(1) mRNA in diabetic rats. These findings suggest that endogenous endothelin and EGF may play a role in diabetes-induced vascular hypertrophy and that mast cells may be pathogenetically involved in this process.

Animals↗
PubMed2000

Influence of glycogen storage on vascular smooth muscle metabolism.

The role of glycogen as an oxidative substrate for vascular smooth muscle (VSM) remains controversial. To elucidate the importance of glycogen as an oxidative substrate and the influence of glycogen flux on VSM substrate selection, we systematically altered glycogen levels and measured metabolism of glucose, acetate, and glycogen. Hog carotid arteries with glycogen contents ranging from 1 to 11 micromol/g were isometrically contracted in physiological salt solution containing 5 mM [1-(13)C]glucose and 1 mM [1, 2-(13)C]acetate at 37 degrees C for 6 h. [1-(13)C]glucose, [1, 2-(13)C]acetate, and glycogen oxidation were simultaneously measured with the use of a (13)C-labeled isotopomer analysis of glutamate. Although oxidation of glycogen increased with the glycogen content of the tissue, glycogen oxidation contributed only approximately 10% of the substrate oxidized by VSM. Whereas [1-(13)C]glucose flux, [3-(13)C]lactate production from [1-(13)C]glucose, and [1, 2-(13)C]acetate oxidation were not regulated by glycogen content, [1-(13)C]glucose oxidation was significantly affected by the glycogen content of VSM. However, [1-(13)C]glucose remained the primary ( approximately 40-50%) contributor to substrate oxidation. Therefore, we conclude that glucose is the predominate substrate oxidized by VSM, and glycogen oxidation contributes minimally to substrate oxidation.

Acetates↗
PubMed1998

Damage to human muscle from eccentric exercise after training with concentric exercise.

1. It is known that a period of eccentric exercise provides protection against damage to muscle from subsequent eccentric exercise. Here we ask, does concentric exercise do the opposite, make muscle more prone to damage? 2. The triceps surae muscle group of one leg in each of eight human subjects was subjected to 30 min of concentric exercise per day, for 5 days. At the end of the training period there was a small but significant increase in passive torque in the exercised muscle (P < 0.05), with no changes in the untrained muscle. 3. After a single period of eccentric exercise, angle-torque curves for muscles of both legs shifted in the direction of longer muscle lengths, suggestive of an increase in series compliance. The shift in the concentrically trained muscle was significantly greater over the first 48 h post-exercise (P < 0. 05). 4. The volume of the trained leg increased significantly more than the untrained leg for five subjects over 72 h post-exercise (P < 0.05). Peak torque fell, passive stiffness increased and both muscles became sore, but with no significant differences between the two legs. 5. It is concluded that a period of concentric exercise increases the susceptibility of muscle to changes associated with the damage from eccentric exercise.

Adult↗
PubMed1998

Impulsivity and history of drug dependence.

Impulsivity was contrasted between 32 subjects with a history of drug-dependence (DRUG+) and 26 subjects with no drug use history (DRUG-) using both behavioral and self-report measures. The hypothesis was that the DRUG+ group would be more impulsive than the DRUG- group. Subjects in the DRUG+ group self-reported more of a tendency toward impulsivity than the DRUG- group in the situations posed in questionnaires. In the behavioural paradigm involving a choice between a smaller intermediate reward and a larger but delayed reward, DRUG+ subjects selected the impulsive option more often, but these differences were not significant. The DRUG+ and DRUG- groups did differ on the mean delay interval for the larger reward, indicating less ability to tolerate longer delays for the larger reward. A frequency distribution of delay intervals for the larger reward indicated that DRUG+ subjects were more likely to maintain very short intervals and less likely to maintain longer intervals.

Adult↗
PubMed1998

Effects of 2,3-butanedione monoxime (BDM) on calcium channels expressed in Xenopus oocytes.

1. We examine the actions of a chemical phosphatase, 2,3-butanedione monoxime (BDM), on endogenous and expressed Ca2+ channel currents in Xenopus oocytes. In previous studies on L-type Ca2+ channel currents in cardiomyocytes and dorsal root ganglia, the inhibitory effects of BDM were attenuated by activation of protein kinase A. 2. Ba2+ currents (IBa) through a human wild-type L-type Ca2+ channel complex (i.e. halpha1C, alpha2-deltaa and hbeta1b) are inhibited by BDM with an IC50 of 16 mM, with 10 mM producing a 36.1 +/- 2.2 % inhibition. IBa through endogenous oocyte N-type Ca2+ channels, upregulated by exogenous alpha2-deltaa and hbeta1b subunits, are inhibited to a similar degree by BDM. 3. To examine whether the action of BDM is dependent on PKA-dependent phosphorylation, a clone of halpha1C deficient in all five serine PKA consensus sites (halpha1C-SA5) was co-expressed with alpha2-deltaa and the human cardiac hbeta3 subunit, which naturally lacks PKA consensus sites. This complex exhibited a sensitivity to BDM that was similar to the wild-type complex, with 10 mM BDM producing 31.6 +/- 1.5 % inhibition. 4. As limited proteolysis upregulates Ca2+ channels in cardiomyocytes and renders them less sensitive to BDM, experiments were performed with a carboxyl terminus deletion mutant, halpha1C-Delta1633. IBa through this subunit showed a sensitivity to BDM that was similar to the wild-type complex, with 10 mM BDM producing 31.3 +/- 1.4 % inhibition. However, co-expression with alpha2-deltaa and hbeta3 subunits reduced potency, and is reflected by an increased IC50 of 22.7 mM. 5. The actions of BDM were examined on a rat brain rbA-1 Ca2+ channel clone, alpha1A, co-expressed with alpha2-deltab and beta1b subunit homologues from rat brain. BDM inhibited the current through this channel complex to a similar degree to that seen for cardiac wild-type channels, with 10 mM BDM causing a 33.1 +/- 3.5 % inhibition. 6. The effects of BDM were compared at two holding potentials, -80 and -30 mV, using the halpha1C-Delta1633, alpha2-deltaa and hbeta3 subunit combination. At -30 mV BDM is more potent with 10 mM BDM reducing IBa by 39.8 +/- 2.7 %, compared with 20.8 +/- 2.2 % at -80 mV. 7. The data suggest that BDM may not exert its inhibitory action by means of a chemical phosphatase effect, but by channel block. The similar potency observed between alpha1C, alpha1A and endogenous (N-type) channels may help point towards a possible site of action; differences with the carboxyl deletion mutant may help further to define a locus of interaction.

Animals↗
PubMed1998

Effects of temperature on human L-type cardiac Ca2+ channels expressed in Xenopus oocytes.

Temperature normally affects peak L-type Ca2+ channel (CaCh) current with a temperature coefficient (Q10) of between 1.8 and 3.5; in cardiomyocytes attenuating protein kinase A activity increases Q10 whilst activating it lowers Q10. We examine temperature effects using cloned human cardiac CaChs expressed in Xenopus oocytes. Peak inward currents (IBa) through expressed CaChs (i.e. alpha1C alpha2/deltaa beta1b) exhibited a Q10 of 5.8+/-0.4 when examined between 15 and 25 degreesC. The nifedipine-sensitive IBa exhibited a higher Q10 of 8.7+/-0.5, whilst the nifedipine-insensitive IBa exhibited Q10 of 3.7+/-0.3. Current/voltage (I/V) relationships shifted to negative potentials on warming. Using instead a different CaCh beta subunit isoform, beta2c, gave rise to an IBa similar to those expressed using beta1b. We utilized a carboxyl deletion mutant, alpha1C-Delta1633, to determine the temperature sensitivity of the pore moiety in the absence of auxiliary subunits; IBa through this channel exhibited a Q10 of 9.3+/-0.3. However, the Q10 for macroscopic conductance was reduced compared to that of heteromeric channels; decreasing from 5.0 (i.e. alpha1C alpha2/deltaa beta1b) and 3.9 (i.e. alpha1C alpha2/deltaa beta2c) to 2.4 (alpha1C-Delta1633). These observations differ markedly from those made in studies of cardiomyocytes, and suggest that enhanced sensitivity may depend on the membrane environment, channel assembly or other regulatory factors.

Amino Acid Sequence↗
PubMed1998

Attenuation of diabetes-associated mesenteric vascular hypertrophy with perindopril: morphological and molecular biological studies.

Vascular disease is now the major cause of morbidity and mortality in the diabetic population. Our group explored the vascular changes associated with experimental diabetes and examined whether these changes can be ameliorated by angiotensin-converting enzyme (ACE) inhibition. The ACE inhibitor perindopril (PE) was administered to streptozotocin-induced diabetic rats for 24 weeks. At death, mesenteric vessels were perfused in vivo followed by assessment of the vascular architecture by quantitative histomorphometry. In a subgroup of animals, RNA was extracted from the mesenteric vasculature for assessment of gene expression of the prosclerotic cytokine, transforming growth factor beta 1 (TGFbeta1), and the matrix protein, type IV collagen. Diabetes was associated with smooth muscle hypertrophy and extracellular matrix (ECM) accumulation. ECM accumulation, particularly collagen deposition, was observed in the medial and adventitial layers. ACE inhibition prevented mesenteric vascular hypertrophy after 24 weeks of diabetes. In addition, overexpression of TGFbeta1 in the vessels of diabetic animals was prevented by PE treatment. Similarly, type IV collagen mRNA levels were increased in diabetic vessels, and this overexpression was also prevented by PE therapy. In summary, ACE inhibition attenuates many of the vascular changes observed in experimental diabetes and may have important clinical implications as a vasoprotective agent in human diabetes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

A new model of diabetic nephropathy with progressive renal impairment in the transgenic (mRen-2)27 rat (TGR).

BACKGROUND: The tissue renin-angiotensin system (RAS) may modulate the structural and functional changes that occur in the diabetic kidney. METHODS: Hypertensive transgenic (mREN-2)27 rat (TGR) that exhibit increased tissue renin expression were administered streptozotocin (STZ, diabetic) or citrate buffer (non-diabetic) at six weeks of age, and sacrificed 4 and 12 weeks later. Further groups were treated for 12 weeks post-STZ or vehicle with the angiotensin converting enzyme inhibitor, perindopril. Comparisons were made with 18-week-old non-diabetic and diabetic spontaneously hypertensive rats (SHR). RESULTS: In diabetic TGR, the most florid lesion was seen after 12 weeks of STZ, with kidneys exhibiting vacuolated tubules, hylanized arterioles, medullary fibrosis and necrosis and severe glomerulosclerosis. In contrast, only mild glomerulosclerosis was seen in non-diabetic TGR and diabetic SHR. Glomerular filtration rate was increased after four weeks of diabetes in TGR and 12 weeks of diabetes in SHR, but declined by greater than 50% after 12 weeks of diabetes in TGR. In both TGR and SHR, diabetes increased albuminuria but did not modify systolic blood pressure. Renal renin content increased progressively in diabetic TGR, and this was associated with increased renin immunolabeling in the juxtaglomerular apparatus (JGA) and the appearance of renin in proximal convoluted tubules. In contrast, renal renin content and JGA renin immunolabeling were unchanged in diabetic SHR. Perindopril attenuated renal pathology, improved renal function and abolished proximal tubular renin immunolabeling in diabetic TGR. CONCLUSIONS: This is the first report of a diabetic rodent model developing rapid onset renal impairment. Furthermore, this study suggests a role for an activated renal RAS in the acceleration of diabetic renal disease and confirms the benefit of drugs that inhibit this system.

Animals↗
PubMed1998

Angiotensin converting enzyme inhibition and calcium antagonism attenuate streptozotocin-diabetes-associated mesenteric vascular hypertrophy independently of their hypotensive action.

OBJECTIVES: To investigate the relative roles of angiotensin II, bradykinin, and calcium-dependent pathways in the genesis of mesenteric vascular hypertrophy in experimental diabetes. DESIGN: Streptozotocin-induced diabetic Sprague-Dawley rats were randomly allocated to these treatments for 24 weeks: no treatment; ramipril at a hypotensive dose; ramipril plus the bradykinin type 2 receptor blocker icatibant; icatibant alone; ramipril at a low dose; the angiotensin II type 1 receptor antagonist, valsartan; the dihydropyridine calcium antagonist, lacidipine; and the nondihydropyridine calcium antagonist mibefradil. METHODS: Systolic blood pressure was serially measured every 4 weeks by tail-cuff plethysmography. We assessed the vascular architecture in sections of mesenteric arteries obtained after in-vivo perfusion, which were stained with an antibody to alpha-smooth muscle actin. RESULTS: Both blood pressure and the mesenteric arterial wall: lumen ratio were reduced by administration of ramipril, at the high dose, either alone or in combination with icatibant, and also by valsartan. Treatment either with the low dose of ramipril or with the calcium antagonists lacidipine and mibefradil was associated with a decrease in the wall : lumen ratio of the mesenteric arteries without influencing blood pressure. CONCLUSIONS: These findings demonstrate that blockade both of angiotensin II-dependent and of calcium-dependent pathways attenuates mesenteric vascular hypertrophy in experimental diabetes. Furthermore, the antitrophic effects of these antihypertensive agents may be independent of their hypotensive effects.

Actins↗
PubMed1998

Dual inhibition of neutral endopeptidase and angiotensin-converting enzyme in rats with hypertension and diabetes mellitus.

It has been suggested that combined inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) may lower blood pressure more effectively than either treatment alone, independent of the degree of salt and volume status or the activity of the renin-angiotensin system. The effects of NEP inhibition in hypertension associated with diabetes mellitus are largely unknown. We therefore compared ACE inhibition, NEP inhibition, and dual NEP/ACE inhibition in diabetic hypertensive rats. Spontaneously hypertensive rats (SHR) aged 9 to 10 weeks were injected with either streptozotocin (45 mg/kg) or citrate buffer and randomized to receive either the ACE inhibitor captopril (25 mg/kg BID), the NEP inhibitor SCH 42495 (30 mg/kg BID), the dual NEP/ACE inhibitor S 21402 (25 or 50 mg/kg BID), or vehicle by gavage for 4 weeks. A group of diabetic SHR was also allocated to receive the combination of SCH 42495 (30 mg/kg BID) and captopril (25 mg/kg BID). The degree of renal NEP inhibition was determined by autoradiography, and plasma renin activity (PRA) was determined by radioimmunoassay. In diabetic SHR, the dual NEP/ACE inhibitor (50 mg/kg BID), as well as the combination of the NEP inhibitor and the ACE inhibitor, reduced systolic blood pressure more effectively than the ACE inhibitor (P<0.001) or the NEP inhibitor (P<0.001) alone. In nondiabetic SHR, the dual NEP/ACE inhibitor and the ACE inhibitor were equally effective, while the NEP inhibitor had only slight blood pressure lowering effects. Relative heart weight decreased in parallel to the changes in blood pressure. Renal NEP was clearly inhibited (70% to 92%; P<0.001) by both the NEP inhibitor and the dual NEP/ACE inhibitor. Both the ACE inhibitor and the dual NEP/ACE inhibitor increased PRA, but the stimulating effect of dual NEP/ACE inhibition on PRA was less than that observed with ACE inhibition alone (P<0.05). Albuminuria in diabetic SHR was lower during treatment with both the dual NEP/ACE inhibitor (50 mg/kg BID) and the combination of NEP inhibition and ACE inhibition compared with vehicle treatment (P<0.05). In conclusion, the present study shows that hypertension in SHR with streptozotocin-induced diabetes is modulated by natriuretic peptides and thus is sensitive to NEP inhibition. The increased efficacy of dual NEP/ACE inhibition on blood pressure in diabetic SHR, compared with ACE or NEP inhibition alone, suggests that this therapeutic approach may prove beneficial in the treatment of hypertension associated with diabetes mellitus and other forms of volume-dependent hypertension.

Analysis of Variance↗
PubMed1998

Early nephropathy predicts vision-threatening retinal disease in patients with type I diabetes mellitus.

In type I (insulin-dependent) diabetes mellitus, nephropathy may be identified in its early stages by the development of persistent microalbuminuria. This longitudinal study sought to examine the development of vision-threatening retinal disease (VTRD) (proliferative retinopathy and clinically significant macular edema) in such patients with early and evolving diabetic kidney disease. Eighty patients with type I diabetes and at least 8 yr of longitudinal data were identified. Glycated hemoglobin and albumin excretion rate (AER) were measured every 3 mo. Ophthalmologic examination was performed at least yearly. Thirteen patients were identified as having evolving nephropathy by a progressive increase in AER and the presence of microalbuminuria during the study period. Sixty-seven patients remained persistently normoalbuminuric. VTRD developed in eight of 13 (62%) patients with evolving nephropathy compared with five of 69 (7%) patients who were persistently normoalbuminuric (P < 0.001) in the absence of any difference in long-term glycemic control or duration of diabetes between the two groups. Clinically significant macular edema (P < 0.05) and proliferative retinopathy (P < 0.01) were both more common in patients with evolving nephropathy. In such patients, AER was 150 x/divided by 1.7 micrograms/min at the time of laser photocoagulation for VTRD. These data suggest that patients with type I diabetes and evolving nephropathy may be at higher risk of developing VTRD than patients who remain persistently normoalbuminuric despite similar long-term glycemic control and duration of diabetes.

Adult↗
PubMed1998

Expression of transforming growth factor-beta1 and type IV collagen in the renal tubulointerstitium in experimental diabetes: effects of ACE inhibition.

Transforming growth factor-beta (TGF-beta) and the renin-angiotensin system (RAS) have both been implicated in the pathogenesis of glomerulosclerosis in diabetic kidney disease. However, tubulointerstitial pathology may also be an important determinant of progressive renal dysfunction in diabetic nephropathy. In the present study, we investigated tubulointerstitial injury, TGF-beta1 expression, and the effect of blocking the RAS by inhibition of ACE. We randomized 36 male SD rats to control and diabetic groups. Diabetes was induced in 24 rats by administration of streptozotocin; 12 diabetic rats were further randomized to receive the ACE inhibitor ramipril (3 mg/l drinking water). At 6 months, experimental diabetes was associated with tubulointerstitial damage, a 70% increase in expression of TGF-beta1 (P < 0.05 vs. control), and a 120% increase in alpha1 (IV) collagen gene expression (P < 0.01 vs. control). In situ hybridization demonstrated a diffuse increase in both TGF-beta1 and alpha1 (IV) collagen mRNA in renal tubules. In addition, intense expression of both transcripts was noted in regions of focal tubular dilatation. Administration of the ACE inhibitor ramipril prevented tubulointerstitial injury and the overexpression of TGF-beta1 and alpha1 (IV) collagen mRNA. Changes in gene expression were accompanied by parallel changes in immunostaining for TGF-beta1 and type IV collagen. The observed beneficial effects of ramipril on the tubulointerstitium in experimental diabetes suggest that this mechanism may contribute to the therapeutic effect of ACE inhibitors in diabetic nephropathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Subjects with a history of drug dependence are more aggressive than subjects with no drug use history.

Aggressive responding was compared between 29 subjects with a history of substance dependence and 24 subjects with no drug use history, using the Point Subtraction Aggression Paradigm. The hypothesis was that subjects from the substance dependence history group would emit more aggressive responses than subjects with no drug use history. The substance dependence history group emitted more aggressive responses per session than the non drug using group (F(1,49) = 14.867, P = 0.032). These results are consistent with previous studies that have reported an association between aggression and drug abuse or dependence.

Adult↗
PubMed1997

Antisocial personality disorder and aggression in recently abstinent cocaine dependent subjects.

To study the relationship between cocaine abstinence symptoms, personality, and aggression, we used the Point Subtraction Aggression Paradigm (PSAP) to measure aggression in 18 subjects admitted for the treatment of cocaine dependence. Eight subjects met criteria for antisocial personality disorder (ASPD). There was a significant correlation between presence of ASPD and frequency of aggressive responding by stepwise multiple regression. When presence of ASPD was factored out of the correlations, there was no significant relationship between aggressive responding and cocaine craving, withdrawal symptoms, amount of cocaine used, or length of time since use. These preliminary results suggest that in cocaine dependent individuals seeking treatment, current aggression is most dependent on the individual's previous aggressive behavior.

Adult↗
PubMed1997

Salt restriction reduces hyperfiltration, renal enlargement, and albuminuria in experimental diabetes.

The effects of dietary salt restriction on the renin-angiotensin system, glomerular filtration rate (GFR), renal size, and albuminuria were assessed in streptozotocin diabetic rats. Two series of experiments were performed: one short-term with severe salt restriction and the second long-term with moderate salt restriction. The first studied the effect of a very-low-salt diet for 4 weeks on GFR, renal size, and plasma angiotensin II concentration in diabetic and control rats. Diabetic and control male Sprague-Dawley rats received either a very-low-salt (0.005% NaCl) or a normal-salt (0.4% NaCl) diet. Diabetes was associated with a 49% increase in GFR, a 34% increase in kidney weight, and an 85% reduction in plasma angiotensin II when compared with control rats (P < 0.001). Sodium restriction in diabetic rats reduced GFR, restored plasma angiotensin II to control values, and retarded kidney growth when compared with diabetic rats receiving a normal sodium diet. GFR correlated negatively with plasma angiotensin II (r = -0.65, P < 0.001) and positively with kidney weight (r = 0.66, P < 0.001). In the second experiment, serial measurements of albuminuria and GFR were performed in control, diabetic, and salt-restricted (0.05% NaCl) control and diabetic rats over 24 weeks. Albuminuria showed a continuous rise in the diabetic rats when compared with control rats. Salt restriction attenuated the increase in albuminuria over the whole study period as well as reducing blood pressure and kidney weight in the diabetic rats. In conclusion, sodium restriction was associated with a lower GFR and kidney weight after 4 weeks and reduced levels of albuminuria, kidney weight, and blood pressure after 24 weeks in diabetic rats. Salt restriction may have an important role in the prevention and treatment of diabetic nephropathy.

Albuminuria↗
PubMed1997

Role of angiotensin II and bradykinin in experimental diabetic nephropathy. Functional and structural studies.

We explored the relative roles of the suppression of angiotensin II and the prevention of bradykinin degradation in mediating the renoprotective effects of ACE inhibitors in experimental diabetic nephropathy. Over a 24-week period, we studied male Sprague-Dawley diabetic and control rats and Sprague-Dawley diabetic rats treated with the ACE inhibitor ramipril, the angiotensin II-AT1 receptor antagonist valsartan, the bradykinin-B2 receptor antagonist HOE 140 (icatibant), and a combination of ramipril and icatibant. Serial measurements of urinary albumin excretion, blood pressure, and glycated hemoglobin were performed monthly. After 6 months, the animals were killed for the measurement of kidney weight and the assessment of glomerular ultrastructure. Over 24 weeks, urinary albumin excretion showed a continuous rise in the untreated diabetic rats. Both ramipril and valsartan, which were equihypotensive, prevented the increase in urinary albumin excretion over the whole study period. Icatibant therapy did not attenuate the antialbuminuric effect of the ACE inhibitor, nor did it have any effect as the sole therapy. Diabetes was associated with increased glomerular basement membrane thickness, glomerular volume, and total mesangial volume. Both ACE inhibition and angiotensin II receptor antagonism attenuated the glomerular ultrastructural changes to a similar degree. Icatibant did not attenuate the effects of ramipril on glomerular morphology. ACE inhibitors and angiotensin II-AT1 receptor blockers appear to confer similar benefits in experimental diabetic nephropathy, and bradykinin-B2 receptor blockers do not influence this effect. These findings suggest that the blockade of angiotensin II is the major pathway responsible for renoprotection afforded by ACE inhibition in experimental diabetic nephropathy.

Albuminuria↗