[Pharmaceutical training and public health].
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Education, Pharmacy↗
Biomedical subjects
J Ménard
Publications and source records attributed to J Ménard.
[Round table chaired by Laurent Broomhead].
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Biological Products↗
[Characteristics of smokers seeking smoking cessation services: the CDT programme].
INTRODUCTION: The development of smoking cessation clinics in France since 1999 has been accompanied by the setting up of an electronic database to evaluate the appropriateness of these services to the needs of smokers. The aim of this paper is to analyse the characteristics of smokers registered in the smoking cessation services national database. METHODS: A cross-sectional population-based study was conducted in 40 smoking cessation centres from 20 French regions. The study population included 14,574 smokers attending the smoking cessation centres that participated in building a national computerised database during the period 2001-2003. RESULTS: A significant proportion of the study population was female (51.4%), middle-aged (42.8 years), more highly educated (34% had received further education) and employed (68%). Almost half of the population was considered to be highly dependent on tobacco. Thirty-four percent of smokers had a past medical history of cardiovascular or lung disease. A history of depression was found in nearly one third of the population. CONCLUSIONS: Young people and individuals from deprived backgrounds were underrepresented, but smoking cessation services were being accessed by highly-dependent smokers and smokers with tobacco-related diseases services. More targeted smoking cessation strategies should be considered in order to improve access to smoking cessation services by more deprived groups.
Adult↗
Premature discontinuation of clinical trial for reasons not related to efficacy, safety, or feasibility.
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Clinical Trials Data Monitoring Committees↗
Saccadic and smooth-pursuit eye movements in deficit and non-deficit schizophrenia.
We have analyzed eye movement performances in schizophrenics showing primary negative or deficit symptoms (n=16) and non-deficit schizophrenics (n=55), and compared them with those of controls (n=34) in order to study the relationships between negative symptoms and eye movement abnormalities. Patients were subtyped into deficit and non-deficit subgroups using the Schedule for the Deficit Syndrome. Three oculomotor paradigms were used: smooth pursuit, a reflexive saccade paradigm and an antisaccadic task. The smooth pursuit gain was significantly decreased (and the rate of catch-up saccades increased) in schizophrenics as compared with controls, but no difference was observed between patient groups. In the reflexive saccade paradigm, no difference was found between controls and patients, except for latency in deficit patients. In the antisaccade paradigm, the number of errors and the latency of successful antisaccades were significantly increased in schizophrenics as compared with controls. The latency of successful antisaccades in both directions was significantly increased in deficit patients as compared with non-deficit patients. The latency of rightward successful antisaccades was significantly increased as compared with the latency of leftward antisaccades in deficit patients only. However, when patients were classified into negative and non-negative groups using the PANSS, no difference was found in the antisaccade paradigm. Smooth pursuit impairment does not seem to depend on the primary enduring negative symptoms.In deficit schizophrenics, the abnormalities observed in the antisaccadic task are consistent with prefrontal dysfunction, and may suggest parietal lobe dysfunction as well.
Adult↗
Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice.
Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys, colon, salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to beta-adrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries, which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein-kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein-kinin system could be involved in the development or progression of cardiovascular diseases.
Animals↗
Towards promotion, structuring and acknowledgement of patient education activities in France.
As patient education becomes more and more widespread in use among French health professionals, it is also becoming increasingly structured, but remains very heterogeneous depending on practitioners and institutions. For several years, this activity has been integrated into various professions. Training is becoming more frequent, and care providers show a certain willingness for common though on improvement and evaluation of their practices. At the same time, health institutions show an increasing interest in these activities, which they wish to promote. Significant improvements recently observed by them may finally lead to the professional and financial recognition expected by care providers.
Education, Professional↗
Angiotensin I-converting enzyme and metabolism of the haematological peptide N-acetyl-seryl-aspartyl-lysyl-proline.
1. Angiotensin I-converting enzyme (ACE) has two homologous active N- and C-terminal domains and displays activity towards a broad range of substrates. The tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) has been shown to be hydrolysed in vitro by ACE and to be a preferential substrate for its N-terminal active site. This peptide reversibly prevents the recruitment of pluripotent haematopoietic stem cells and normal early progenitors into the S-phase. 2. Angiotensin I-converting enzyme inhibitors, given as a single dose to normal subjects or during long-term treatment in hypertensive patients, result in plasma AcSDKP levels five- to six-fold higher and urine concentrations 40-fold higher than those of control subjects and/or patients. Thus, AcSDKP is a natural peptide hydrolysed by the N-terminal domain of ACE in vivo. In addition, ACE may be implicated in the process of haematopoietic stem cell regulation by permanently degrading this natural circulating inhibitor of cell entry into the S-phase. 3. Besides hydrolysis by ACE, the second very effective mechanism by which AcSDKP is cleared from plasma is glomerular filtration. Because of its high sensitivity and specificity, the measurement of AcSDKP in plasma and urine provides a valuable tool in screening specific inhibitors of the N-terminal domain of ACE and in monitoring ACE inhibition during chronic treatment. 4. The long-term consequences of AcSDKP accumulation are not known. During chronic ACE inhibition in rats, AcSDKP levels slightly increase in organs with high ACE content (kidneys, lungs). To significantly increase its concentration in target haematopoietic organs (the extracellular fraction of bone marrow), AcSDKP has to be infused on top of a captopril-based treatment. 5. A selective inhibitor of the N-domain of ACE in vitro and in vivo has been identified recently. The phosphinic peptide RXP 407 does not interfere with blood pressure regulation, but does increase, dose dependently, plasma concentrations of AcSDKP in mice, in contrast with lisinopril, which affects the metabolism of both AcSDKP and angiotensin I. N-Terminal-selective ACE inhibitors may be used to selectively control AcSDKP metabolism in target haematopoietic organs. This new therapeutic strategy may be of value for protecting haematopoietic cells from the toxicity of cancer chemotherapy.
Angiotensin-Converting Enzyme Inhibitors↗
Risk assessment and treatment benefit in intensively treated hypertensive patients of the hypertension Optimal Treatment (HOT) study.
BACKGROUND: The Hypertension Optimal Treatment (HOT) Study provided information about cardiovascular events in 18,790 hypertensives, subjected to pronounced blood pressure lowering for a mean of 3.8 years. METHODS AND RESULTS: The HOT Study data have been further analysed after risk stratification of the patients (1999 World Health Organization and International Society of Hypertension guidelines criteria): (i) no patients of the HOT Study were classified as low risk, 50% were classified as medium risk, 20.2% as high risk and 29.8% as very high risk; (ii) incidence of cardiovascular events in these patients with excellent blood pressure control [92% had diastolic blood pressure (DBP) < or = 90 mmHg] remained proportional to pretreatment risk. The relative risk of very high- versus medium-risk strata was between two and three both when HOT Study patients were considered independently of, or within the DBP target group they had been randomized to; and (iii) event rates in all risk strata were calculated to be much lower (possibly 60% lower) than rates expected from baseline risk calculated approximately by the Framingham equation. CONCLUSIONS: The low event rate in HOT Study patients is likely to result from pronounced blood pressure lowering, and is not explained by a lower risk profile than in previous controlled trials of antihypertensive treatment. The persistence of a risk gradient despite intensive blood pressure lowering suggests a combination of blood pressure control with other strategies of risk correction and the need to initiate antihypertensive therapy before complications develop.
Aged↗
Effects of aerobic physical exercise in the elderly with type 2 diabetes mellitus.
The objective of this study was to determine the impact of an aerobic physical exercise program in the treatment of a group of elderly patients with type 2 diabetes mellitus (DM) in relation to metabolic control, physical capacity, quality of life (QOL) and attitudes toward diabetes. Patients were randomly assigned to either an experimental (n=19) or a control (n=20) group. The following measurements were conducted at baseline and after week 16: glycosylated hemoglobin (hbA1c), fructosamine, 3 h oral glucose tolerance test, treadmill test (Balke-Naughton), and a questionnaire on QOL and attitudes toward DM. After the intervention, the experimental group showed a significant decrease of glucose excursion during the oral glucose tolerance test (OGTT) (area under the curve) (16.6+/-3.8 vs. 15.3+/-3.1, P<0.05) and an increase in total time on the treadmill (s) (423+/-207 vs. 471+/-230, P<0.05). An improvement in the attitudes toward DM was observed in the experimental group (P=0.01) but not in the control group. Female gender, higher body mass index and hbA1c were factors associated with a response to the intervention. This study suggests that physical exercise has significant effects on glucose excursion during an OGTT and exercise tolerance in elderly patients with type 2 DM.
Journal Article↗
Pilot study of combined blockade of the renin-angiotensin system in essential hypertensive patients.
BACKGROUND: Additive hemodynamic effects of combined blockade of the renin-angiotensin system by an angiotensin I converting enzyme inhibitor and an angiotensin II antagonist have been observed in sodium-depleted normotensive volunteers and in patients with congestive heart failure. OBJECTIVE: To investigate whether the same additive hemodynamic effects occur in patients with hypertension and to verify the safety of such an approach. DESIGN: Multicenter, randomized, double-blind, parallel-group, pilot study. PATIENTS: 177 patients with mild-to-moderate hypertension [diastolic blood pressure (DBP): 95-115 mmHg after a 4-week placebo run-in period] were included in the study. INTERVENTION: Combination therapy consisting of 50 mg losartan daily and 10 mg enalapril daily was administered for 6 weeks. The effects of this therapeutic regimen was compared with similar groups of patients who received either 50 mg losartan daily or 10 mg enalapril daily. MAIN OUTCOME MEASURES: 24-hour ambulatory mean DBP and clinic DBP measured at trough after 6 weeks of treatment. RESULTS: 24-hour ambulatory mean DBP did not significantly differ between treatment groups although the combination tended to lower BP more. The combination therapy was more effective on clinic DBP measured at trough than was losartan by 3.2 mmHg [confidence interval (95%, CI) 0.7-5.7 mmHg, P = 0.012], and more effective than enalapril by 4.0 mmHg (95% CI, 1.5-6.4 mmHg, P = 0.002). In a subgroup of 28 patients, higher plasma active renin and angiotensin I levels during blockade by the combination therapy were observed. This finding confirmed that the combination of the two agents inhibited the renin-angiotensin system to a greater extent than did either agent alone. CONCLUSION: A combination of 10 mg enalapril daily and 50 mg losartan daily safely induces a supplementary, although modest, fall in clinic DBP in patients with mild-to-moderate essential hypertension.
Adolescent↗
Angiotensinogen concentrations and renin clearance : implications for blood pressure regulation.
Renin (REN) requires seconds to convert angiotensinogen (AGT) to angiotensin I. We tested the hypothesis that this long catalytic cycle might indicate an influence of AGT concentrations on REN clearance. We studied 2 transgenic rat (TGR) strains for human (h) AGT; one strain has hAGT values approximately 7-fold higher than the other (68+/-18 versus 10+/-4 microg angiotensin I/mL). hREN (30 000 pg) was bolus-infused into both lines and into nontransgenic controls. The terminal half-life (T1/2beta) was increased (130 versus 82 minutes) and the metabolic clearance rate (MCR) was decreased (0.83+/-0.29 versus 2.2+/-0.66 microL. min(-1). g(-1)) in the high hAGT strain compared with the low hAGT strain. The difference was not related to volume of distribution at steady state. Infused hREN blocked with remikiren resulted in T1/2beta and MCR values that were not different from control values. Infused unblocked and blocked radiolabeled hREN was distributed similarly in the hAGT TGR strains. Infused mouse REN, which cannot convert hAGT, had similar T1/2beta and MCR values in hAGT TGR. Measuring REN with direct radioimmunoassay or by enzyme kinetic assay gave similar results. We next crossed homozygous hAGT TGR from both strains with homozygous hREN TGR. Heterozygous offspring from the low hAGT TGR strain had plasma REN activity, hREN concentration, and rat AGT values that were no different from those of their parents. However, TGR offspring with high hAGT values had massively elevated plasma REN activity and hREN concentration as well as elevated blood pressure, even though both the hREN and rREN genes are downregulated. We conclude that increased AGT concentrations decrease REN MCR and increase REN T1/2beta. The REN-AGT complex may stabilize plasma REN concentration and regulate plasma REN activity independent of renal REN secretion and angiotensin II-mediated feedback. These effects could augment angiotensin I generation and influence blood pressure. The notion that AGT is merely a passive substrate reservoir for REN should be revised.
Angiotensin I↗
Influence of the M235T polymorphism of human angiotensinogen (AGT) on plasma AGT and renin concentrations after ethinylestradiol administration.
The T235 allele of the angiotensinogen (AGT) gene is associated with plasma AGT concentration and pregnancy-induced hypertension. The aim of this study was to compare changes in the circulating renin-angiotensin system after short-term (2 days) and repeated (7 days) administration of 50 microg ethinylestradiol (EE) in homozygous normotensive men (TT and MM). After repeated EE administration, renin stimulation was induced by a single oral dose of 40 mg furosemide, followed by 50 mg captopril, 12 h later. The short-term administration of EE did not induce a significant differential genotype-dependent increase in AGT concentration. In the 7-day study, TT subjects had higher peak plasma AGT concentrations than MM subjects. The more pronounced AGT increase in TT subjects resulted in similar plasma renin activity at a lower plasma active renin concentration, with a higher plasma renin activity/active renin ratio. The difference between genotypes in renin secretion resulted in readjustment of angiotensins production. In conclusion, the T235 allele of the AGT gene is associated with greater stimulation of AGT secretion in plasma after EE administration. In the short-term, complete readjustment of the circulating renin-angiotensin system occurs, through a decrease in renin release, which blunts the effects of the increase in AGT concentration.
Adolescent↗
Distribution of Salmonella in swine herds in Québec.
Five porcine finishing units, previously identified as contaminated by Salmonella, were sampled to identify possible sources of contamination and to study the distribution of Salmonella within the herds. A total of 208 environmental samples were taken and 87 samples (42%) were found contaminated by Salmonella spp. Salmonella was recovered from several types of samples. Among these, fecal material from pens, building environment such as doors, floors, ventilation units, dust and farm accessories were most often found positive. Some of the flies and rodents were also positive. Two of the finishing units were part of an integrated production system and the prevalence and distribution of Salmonella spp. at different production steps of the integrated facilities were studied. Forty-one farms were sampled and a total of 1923 faecal samples in randomly selected pens were analysed. One hundred and fifty-one samples (7.9%) were positive for Salmonella spp. Among the farms sampled, 70.7% (29/41) were positive for isolation of Salmonella. The different levels in the integrated production were unevenly contaminated. Replacement sow (15.9%) and finishing unit for gilts (21.9%) were the most contaminated levels. Ten serotypes of Salmonella (n = 132) were identified in the production pyramid with a predominance of Salmonella Derby (37.1%) and Salmonella Typhimurium (34.1%). Pulse Field Gel Electrophoresis analysis of the various isolates from serotypes and Salmonella Typhimurium, Salmonella Derby and Salmonella Anatum showed no variation in the genetic profiles, within each serotype, suggesting a vertical contamination throughout the different production steps.
Agglutination Tests↗
Pharmacodynamic effects of dual neutral endopeptidase-angiotensin-converting enzyme inhibition versus angiotensin-converting enzyme inhibition in humans.
BACKGROUND: There is currently no clear evidence that dual neutral endopeptidase-angiotensin-converting enzyme inhibitors have effects on angiotensin-converting enzyme, renin, or blood pressure that are different from specific angiotensin-converting enzyme inhibitors in humans. METHODS AND RESULTS: In a double-blind, placebo-controlled crossover study, single oral doses of the dual neutral endopeptidase-angiotensin-converting enzyme inhibitor, 10 mg BMS-186716 and the angiotensin-converting enzyme inhibitor fosinopril (20 mg) were administered to 9 normotensive subjects with induced mild sodium depletion. Values for area under the time curve from 0 to 24 hours [AUC(0-24)] for the plasma angiotensin II/angiotensin I ratio and for angiotensin II were similar for 10 mg BMS-186716 and 20 mg fosinopril. Plasma atrial natriuretic peptide decreased significantly after 20 mg fosinopril (9+/-3 pg/mL; P < .05 versus 10 mg BMS-186716 and placebo) compared with 10 mg BMS-186716 (16+/-5 pg/mL) and placebo (16+/-5 pg/mL). BMS-186716, 10 mg, significantly increased urinary atrial natriuretic peptide from baseline by 2+/-1.3-fold (P < .05 versus placebo and 20 mg fosinopril). AUC(0-24) of plasma active renin did not differ significantly between 10 mg BMS-186716 (3898+/-333 pg x h x mL(-1)) and 20 mg fosinopril (4383+/-302 pg x h x mL(-1); difference not significant). Both drugs decreased blood pressure, but the AUC(0-24) of the changes in mean blood pressure differed significantly from placebo (79+/-84 mm Hg x h) only for 20 mg fosinopril (181+/-6 mm Hg x h; P < .05) but not for 10 mg BMS-186716 (118+/-7 mmHg x h). CONCLUSIONS: In this model, single oral doses of 10 mg BMS-186716 and 20 mg fosinopril induced similar 24-hour in vivo angiotensin-converting enzyme inhibition. BMS-186716, 10 mg, increased urinary atrial natriuretic peptide and blunted the expected decrease in plasma atrial natriuretic peptide caused by angiotensin-converting enzyme inhibition. BMS-186716, 10 mg, did not inhibit plasma active renin rise compared with 20 mg fosinopril. A single oral dose of 10 mg BMS-186716 had a shorter blood pressure-lowering effect than 20 mg fosinopril.
Administration, Oral↗
Pharmacokinetic-pharmacodynamic interactions of candesartan cilexetil and losartan.
BACKGROUND: The variability of the blood pressure response to blockade of the angiotensin II type 1 receptor is influenced by renin status and pharmacokinetics and pharmacokinetic-pharmacodynamic interactions. OBJECTIVE: To compare the pharmacokinetic-pharmacodynamic interactions of two doses of an ester prodrug of a noncompetitive angiotensin II type 1 receptor antagonist, candesartan cilexetil, at 8 and 16 mg, with those of the reference angiotenisn II type 1 receptor blocker, losartan, at the standard dose (50 mg), in a human model that controls renin status. DESIGN AND METHODS: In a double-blind placebo-controlled crossover study, we compared the effects on renin and mean blood pressure over 24 h of single oral doses of candesartan cilexetil at 8 and 16 mg and losartan at 50 mg in 16 sodium-depleted normotensive subjects. RESULTS: The area under the curve (0-24 h) for plasma active renin did not differ significantly between 8 mg candesartan cilexetil and 50 mg losartan, but was significantly higher for 16 than for 8 mg candesartan cilexetil or for 50 mg losartan. The area under the curve (0-24 h) for the fall in mean blood pressure with 16 mg candesartan cilexetil (-197 +/- 96 mmHg/h) was significantly greater than that for placebo (-112 +/- 81 mmHg/h; P< 0.05) but the difference was not statistically significant compared with either 8 mg candesartan cilexetil (-158 +/- 95 mmHg/h) or 50 mg losartan (-144 +/- 66 mmHg/h). The area under the curve (0-24 h) for the fall in mean blood pressure did not significantly differ between 8 mg candesartan cilexetil, 50 mg losartan and placebo. The area under the curve (0-24 h) for plasma active renin was significantly correlated to that for plasma levels of the active metabolite of losartan, EXP 3174 (r = 0.65, n = 16, P< 0.01). No such correlation was detected for each single dose of candesartan cilexetil but a dose-response relationship was present when both doses were combined. CONCLUSIONS: The pharmacodynamic effects of a single oral dose of 16 mg candesartan cilexetil are greater than those of 50 mg losartan and 8 mg candesartan cilexetil. The variability in the pharmacokinetic-pharmacodynamic interaction is less pronounced for candesartan than for EXP 3174, which could result in reduced variability of the blood pressure effects in patients.
Administration, Oral↗
Renal and metabolic clearance of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) during angiotensin-converting enzyme inhibition in humans.
We investigated the contributions of angiotensin-converting enzyme (ACE) and glomerular filtration to creating the new metabolic balance of the hemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) that occurs during acute and chronic ACE inhibition in healthy subjects. We also studied the effect of chronic renal failure on the plasma concentration of AcSDKP during long-term ACE inhibitor (ACEI) treatment or in its absence. In healthy subjects, a single oral dose of 50 mg captopril (n=32) and a 7-day administration of 50 mg captopril BID (n=10) resulted in a respective 42-fold (range, 18- to 265-fold) and 34-fold (range, 24-fold to 45-fold) increase in the ratio of urinary AcSDKP to creatinine accompanied by a 4-fold (range, 2- to 6.8-fold) and 4.8-fold (range, 2.6- to 11.8-fold) increase in plasma AcSDKP levels. Changes in plasma AcSDKP and in vitro ACE activity over time showed an intermittent reactivation of ACE between each captopril dose. In subjects with chronic renal failure (creatinine clearance<60 mL/min per 1.73 m2), plasma AcSDKP levels were 22 times higher (95% confidence interval, 15 to 33) in the ACEI group (n=35) than the control group (n=23); in subjects with normal renal function, they were only 4.1 times higher (95% confidence interval, 3.2 to 5.3) in the ACEI group (n=19) than the non-ACEI group (n=21). Renal failure itself led to a slight increase in plasma AcSDKP concentration. In conclusion, intermittent reactivation of ACE between doses of an ACEI is the major mechanism accounting for the lack of major AcSDKP accumulation during chronic ACE inhibition in subjects with normal renal function.
Adult↗
Contrasting effects of selective T- and L-type calcium channel blockade on glomerular damage in DOCA hypertensive rats.
Mibefradil and amlodipine are calcium antagonists with different channel selectivities. Mibefradil blocks both L- and T-type calcium channels; although in the usual pharmacological doses, it predominantly blocks the T-type channels. In contrast, amlodipine selectively blocks L-type channels. The goal of the present study was to assess whether this differential selectivity would result in different effects on end-organ damage in experimental hypertension. For this purpose, deoxycorticosterone acetate (DOCA)-salt hypertensive rats were treated either with equipotent doses of mibefradil or amlodipine (30 mg. kg(-1). d(-1) as food admix). Despite the fact that both drugs decreased systolic arterial pressure to the same extent (140+/-5 mm Hg in the mibefradil group and 144+/-3 mm Hg in the amlodipine group versus 225+/-5 mm Hg in the untreated-DOCA group), only mibefradil decreased proteinuria (35. 5+/-6.5 versus 103.3+/-14.1 mg/24 h in untreated DOCA-salt animals) and prevented glomerular lesions. Both drugs, however, prevented the occurrence of vascular renal lesions. To elucidate the mechanism responsible for this difference, we evaluated in an additional series of experiments the effects of mibefradil and amlodipine on plasma and renal renin concentrations, as well as the effects of the addition of enalapril, an ACE inhibitor, given on top of both drugs on proteinuria. Amlodipine, in contrast to mibefradil, markedly stimulated the plasma (17.8+/-2.6 ng Ang I. mL(-1). h(-1) in the amlodipine group versus 3.9+/-0.4 ng Ang I. mL(-1). h(-1) in the mibefradil group and 3.2+/-0.3 ng Ang I. mL(-1). h(-1) in the untreated-DOCA group) and renal (2.42+/-0.37 ng Ang I. mL(-1). h(-1) in the amlodipine group versus 0.36+/-0.04 ng Ang I. mL(-1). h(-1) in the mibefradil group and 0.26+/-0.08 ng Ang I. mL(-1). h(-1) in the untreated-DOCA group) renin concentrations. Stimulation of the renin-angiotensin system could explain the absence of a renal protective effect of amlodipine. This was also suggested by the fact that enalapril given in addition to amlodipine could decrease proteinuria. In conclusion, T-type channel blockade by mibefradil decreases blood pressure without stimulation of the renin-angiotensin system and therefore prevents most of the glomerular damage in DOCA hypertensive rats.
Amlodipine↗