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R Testa

Publications and source records attributed to R Testa.

At least 91 records · Page 5Linked to original sources
PubMed1998

Effects of reduced glutathione and n-acetylcysteine on lidocaine metabolism in cimetidine treated rats.

The aim of this work was to evaluate the effects of exogenous glutathione (GSH) and N-acetylcysteine (NAC) on the formation of monoethylglycinexylidide (MEGX) from lidocaine in rats with and without the administration of cimetidine. GSH and NAC were administered intraperitoneally (i.p.) (1 mmol/kg) 1 hour before treatment with cimetidine (0.5 mmol/kg) or saline, and 1 hr later all rats were injected i.p. with lidocaine (1 mg/kg). Blood samples were drawn 30 min after the lidocaine injection. MEGX and lidocaine serum concentrations were determined by means of fluorescence polarization immuno-assay using the TDX system. Cimetidine produced a decrease in MEGX levels (from 210 +/- 18 to 164 +/- 13 ng/mL) and a parallel increase in lidocaine levels (from 73 +/- 22 to 172 +/- 47 ng/mL), consistent with cytochrome P-450 3A inhibition. Both GSH and NAC produce a significant decrease in MEGX levels (151 +/- 16 and 139 +/- 14 ng/mL, respectively), but no significant increase in lidocaine levels were found. As compared to the cimetidine group, pre-treatment using either GSH or NAC with cimetidine produced a marked decrease in lidocaine levels (37 +/- 27 and 63 +/- 28 ng/mL, respectively) and no modification of MEGX levels (155 +/- 12 and 165 +/- 22 ng/mL, respectively). These results suggest that GSH and NAC might accelerate the lidocaine metabolism while counteracting the inhibitory effect of cimetidine.

Acetylcysteine↗
PubMed1998

Wilson's disease with concomitant beta thalassaemia and factor V deficiency.

A case of late presentation of Wilson's disease in a female with a thalassaemic trait is reported in whom diagnosis of Factor V deficiency was made. Despite ignoring the disease for years the patient had compensated cirrhosis. She had a dramatic family history of Wilson's disease affecting at least two brothers and two sisters. Moreover, her haematologic problems were not clinically revealed until diagnosis had been made on the basis of suspicions arising from laboratory results. The therapy of choice for hepatolenticular degeneration was not feasible due to the patient's refusal. Zinc salts were, therefore, administered. To our knowledge the association of such rare genetic disorders has not been reported.

Factor V Deficiency↗
PubMed1997

Presence of hemoglobinopathies in Sicily: a historic perspective.

Sicily, at the center of the Mediterranean, has been the meeting place of Eastern and Western civilizations, and in the Sicilian population the presence of many different alterations in the globin gene clusters can surely be considered testimony of past colonizations. From 1975 to 1994, 100,000 Sicilian subjects were screened by us to monitor the presence of hemoglobin (Hb) structural variants. In this paper we present the data gathered, emphasizing the high incidence (2.5%) of carriers of at least one abnormal Hb, and the great heterogeneity of globin molecular defects on the island. Twenty-six different mutations were identified: the most common occur in the beta-globin gene (beta(S), beta(C), deltabeta(Lepore), beta(G-San José), beta(O-Arab), but also quite frequent is the mutated allele alpha(J-Oxford). The chromosome haplotypes associated with some of them were characterized. Two uncommon Hbs, Copenhagen and D Punjab, and some 18 rare variants complete the wide spectrum of structural alterations of globin genes in Sicily. We think they are de novo mutations prevalently. It is not possible to exclude that the presence of a few of them is related to migratory phenomena, particularly from North Africa and East Asia. Numerous thalassemic alleles complete the picture of globin gene mutations in Silicy.

Adolescent↗
PubMed1997

Antagonism to noradrenaline-induced lethality in rats is related to affinity for the alpha1A-adrenoceptor subtype.

The potency of several alpha1-adrenoceptor antagonists in preventing the noradrenaline-induced lethality in conscious rats, their binding affinity for the native alpha1A- and alpha1B-adrenoceptors, the recombinant animal alpha1a-, alpha1b- and alpha1d-adrenoceptor subtypes, as well as their functional affinity for the alpha1L-adrenoceptor subtype were evaluated. The potency of the tested compounds as antagonists of noradrenaline-induced lethality was correlated with the affinity for the alpha1A- (and alpha1a-) adrenoceptor subtype, but not with the affinity for the other subtypes. On the contrary, the hypotensive effects of the compounds, assessed in anesthetized rats, were not clearly related with the affinity for any of the alpha1-subtypes. These results suggest that the alpha1A-subtype plays a determining role in preventing lethality induced by noradrenaline in the rats, and that this activity is unrelated to the hypotensive effect of the compounds, which cannot be clearly correlated with affinity for a particular alpha1-adrenoceptor subtype.

Adrenergic alpha-Antagonists↗
PubMed1997

Alpha 1-adrenoceptor subtype selectivity: molecular modelling and theoretical quantitative structure-affinity relationships.

This study constitutes a preliminary rationalization, at the molecular level, of antagonist selectivity towards the three cloned alpha 1-adrenergic receptor (alpha 1-AR) subtypes. Molecular dynamics simulations allowed a structural/dynamics analysis of the seven alpha-helix-bundle models of the bovine alpha 1a-, hamster alpha 1b-, and rat alpha 1d-AR subtypes. The results showed that the transmembrane domains of these subtypes have different dynamic behaviours and different topographies of the binding sites, which are mainly constituted by conserved residues. In particular, the alpha 1a-AR binding site is more flexible and topographically different with respect to the other two subtypes. The results of the theoretical structural/dynamics analysis of the isolated receptors are consistent with the binding affinities of the 16 antagonists tested towards the three cloned alpha 1-AR subtypes. Moreover, the theoretical quantitative structure-affinity relationships obtained from the antagonist-receptor interaction models further corroborates the hypothesis that selectivity towards one preferential subtype is mainly modulated by receptor and/or ligand distortion energies. In other words, subtype selectivity seems to be mainly guided by the dynamic complementarity (induced fit) between ligand and receptor. On the basis of the quantitative models presented it is possible to predict both affinities and selectivities of putative alpha 1-AR ligands as well as to estimate the theoretical alpha 1-AR subtype affinities and selectivities of existing antagonists.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1997

The acrosome reaction response assay: a new way to identify patients in whom pentoxifylline would improve the human follicular fluid-induced acrosome reaction.

The effect of pentoxifylline on the spontaneous and follicular fluid (hFF)-induced acrosome reaction (AR) was studied in an attempt to identify those patients who would benefit from the use of pentoxifylline as an AR-stimulating agent. Pentoxifylline (1 mg/ml) produced no significant increase over spontaneous AR at any of the time points studied (60 min: 6.2% +/- 2.0 spontaneous AR vs 7.4% +/- 2.0 pentoxifylline AR; 120 min: 7.1% +/- 1.6 spontaneous vs 9.0% +/- 2.5 pentoxifylline; 180 min: 7.0% +/- 1.8 spontaneous vs 10.9% +/- 4.0 pentoxifylline, n = 6). On the other hand, hFF produced a significant increase in AR (6.9% spontaneous AR vs 11.2% hFF AR, p < 0.001, n = 39) and this effect was enhanced by pre-incubation with pentoxifylline (15.0% pentoxifylline + hFF AR vs 11.2% hFF AR, p < 0.001). There were no differences in percentage AR induced by hFF or pentoxifylline + hFF between patients with normal (n = 16) and abnormal (n = 25) semen samples. Individual analysis of the effects of hFF and pentoxifylline + hFF on AR showed great variability between patients and enabled us to classify them into four categories: inducible-responder (15%), non-inducible-responder (23%), inducible-non-responder (41%) and non-inducible-non-responder (21%). An induction index (II) (induction produced by hFF divided by spontaneous AR) and a response index (RI) (induction produced by pentoxifylline + hFF divided by hFF) were calculated for each sample. Patients previously classified as inducible exhibited an II > 0.30 and patients previously classified as responders showed an RI > 0.26. There was no correlation between II and RI values (Spearman, r = -0.185, p = 1). Our results show that pentoxifylline is an enhancer of the induced AR only in some patients. We propose an 'AR response assay' to identify responder patients and thus enable rational use of this drug.

Acrosome↗
PubMed1997

Relative levels of alpha-, beta-, and gamma-mRNA from patients with severe and intermediate beta-thalassemia major.

We have determined the relative quantities of gamma- and beta-mRNAs and the alpha/beta-mRNA ratios in 37 patients with beta-thalassemia major with specific genotypes, namely 8 with a homozygosity for codon (CD) 39 (C-->T), 7 with a homozygosity for IVS-I-110 (G-->A), 5 with a homozygosity for IVS-I-6 (T-->C), for 15 patients with compound heterozygosities for 2 of these 3 mutations, and for 2 patients with the IVS-I-110 (G-->A)/-87 (C-->G) mutations. None had an alpha-thalassemia. Twelve patients had thalassemia intermedia and the remainder, transfusion-dependent severe conditions. Differences in phenotype were observed for compound heterozygotes involving the IVS-I-6 (T-->C) mutation in combination with either the IVS-I-110 (G-->A) or the CD 39 (C-->T) mutations: patients with thalassemia intermedia had a lower alpha/beta-mRNA ratio, about half of that of the patients with severe beta-thalassemia major. This might suggest a higher beta-mRNA synthesis in some patients than in others with the same genotype; mutations in promoter, enhancer, and/or locus control region sequences may be responsible for these differences. In vitro chain synthesis data were too incomplete to be helpful in this study. The RT-PCR procedure allowed the separation of abnormal (extended) mRNA from normal beta-RNA in subjects carrying the IVS-I-110 (G-->T) mutation. The relative quantities of this beta Th-mRNA (% of beta A + beta Th) were determined by scanning of the appropriate autoradiograms; they averaged 25% for homozygotes and about 4% for heterozygotes, indicating a considerable instability of the message.

Codon↗
PubMed1997

Determination of vanillylmandelic, 5-hydroxyindoleacetic and homovanillic acid in urine by isocratic liquid chromatography.

A new isocratic HPLC method, employing electrochemical detection, is described for the determination of urinary vanillylmandelic acid, 5-hydroxyindoleacetic acid and homovanillic acid. The main advantages of this technique are: simplicity, simultaneous determination of all analytes, the absence of an extraction procedure, isocratic elution and low cost. The diluted urine is injected onto a C18 reversed phase column. The mobile phase is potassium dihydrogenphosphate buffer containing 1-heptanesulphonic acid, methanol and acetonitrile. The calibration curves are linear from 0.1 to 50 mg/l; the precision data show CV less than 2.36% for within-day assay and less than 2.72% for day-to-day assays. The mean recoveries for supplemented samples are 98.2 to 102.0% for vanillylmandelic acid, 99.6 to 103.9% for 5-hydroxyindoleacetic acid and 98.7 to 102.0% for homovanillic acid. In comparisons of the present method with Radjaipur's extraction method (Radjaipur M. et al., Eur J Clin Chem Clin Biochem 1994; 32:609-13) the slopes for the three analytes were nearly 1, and the confidence region of the intercepts was close to 0. In conclusion the technique seems to be suitable for routine determination of the three analytes, especially for mass screening purposes.

Adult↗
PubMed1997

Pharmacological characterization of the uroselective alpha-1 antagonist Rec 15/2739 (SB 216469): role of the alpha-1L adrenoceptor in tissue selectivity, part I.

Alpha adrenoceptor antagonists have been convincingly shown to be beneficial in reducing both subjective and objective indices of urethral obstruction in benign prostatic hyperplasia. Rec 15/2739 (SB 216469) is a novel alpha-1 adrenoceptor (alpha-1 AR) antagonist currently being developed for benign prostatic hyperplasia. When evaluated in radioligand binding assays with expressed animal or human alpha-1 ARs, Rec 15/2739 shows marked to moderate selectivity for the alpha-1a AR subtype. Its affinity for the recombinant alpha-2 AR subtypes or native dopaminergic D2 receptor was about 100-fold lower than that for alpha-1a AR subtype. In canine tissues, Rec 15/2739 was 20-fold more potent as an inhibitor of [3H]prazosin binding to prostate vis-a-vis aorta. Functional studies in isolated rabbit tissues also confirmed the uroselectivity of Rec 15/2739, with substantially higher affinity (Kb = 2-3 nM) being observed in urethra and prostate, compared with ear artery and aorta (Kb = 20-100 nM). The in vitro selectivity observed with Rec 15/2739 was confirmed in vivo in the anesthetized dog, comparing potency against norepinephrine- or hypogastric nerve stimulation-induced urethral contraction with its ability to reduce diastolic blood pressure. In this model, Rec 15/2739 had greater selectivity than any other alpha-1 AR antagonist examined, including terazosin and tamsulosin. Based on the low potency of prazosin and some of its structural analogs in the rabbit and dog lower urinary tract tissues, it appears that norepinephrine contracts these tissues via activation of the alpha-1L AR. Hence this alpha-1 AR subtype, rather than the alpha-1A AR, may mediate the contraction in vivo.

Adrenergic alpha-Antagonists↗
PubMed1997

Pharmacological characterization of the uroselective alpha-1 antagonist Rec 15/2739 (SB 216469): role of the alpha-1L adrenoceptor in tissue selectivity, part II.

The aim of the present work was to investigate whether or not the uroselectivity of Rec 15/2739 and several other alpha-1 adrenoceptor (alpha1-AR) antagonists observed in the anesthetized dog could be related to selectivity of these compounds for a particular alpha-1 AR subtype. The binding affinity of the tested compounds for canine prostate alpha-1 ARs and their in vitro functional affinity for the alpha-1 ARs of rabbit urethra and prostate correlated with their functional affinity for the alpha-1L AR subtype, but not with the binding affinity for recombinant animal and human alpha-1a, alpha-1b and alpha-1d AR subtypes. Similar results were obtained when the in vivo potency on urethral pressure was correlated with the affinity for the alpha-1 AR subtypes; also in this case alpha-1L AR gave the best correlation. No correlation was obtained by considering the other alpha-1 AR subtypes. The in vivo hypotensive effects observed in dog after i.v. administration of the considered compounds correlated only with the binding affinity for the animal and human alpha-1d subtype. In conclusion, the results shown in the present paper indicate that the potencies of different alpha-1 antagonists against the contractions induced by norepinephrine on tissues of the lower urinary tract of rabbits and dogs are better correlated with their affinity for the putative alpha-1L subtype than for the alpha-1a subtype. Only the compounds showing selectivity for the alpha-1L subtype versus the alpha-1d subtype proved highly selective in vivo for the lower urinary tract versus the vascular tissues.

Adrenergic alpha-Antagonists↗
PubMed1997

Monoethylglycinexylidide formation measurement as a hepatic function test to assess severity of chronic liver disease.

OBJECTIVES: Monoethylglycinexylidide (MEGX) is the main lidocaine metabolite and its formation depends on liver microsomal activity. MEGX formation was studied in comparison with the histological score of chronic hepatitis and with the clinical score (Child-Pugh) of cirrhosis. Furthermore, we evaluated its ability to distinguish between the two liver diseases. METHODS: We studied 284 patients: 130 with chronic hepatitis (on the basis of the histological activity index, 45 had mild chronic hepatitis, 54 had moderate chronic hepatitis, and 31 had chronic hepatitis with cirrhosis) and 154 with cirrhosis (49 Child-Pugh's class A, 78 class B, and 27 class C). MEGX formation was evaluated 15, 30, and 60 min after lidocaine administration. RESULTS: MEGX formation showed a stepwise decline corresponding to worsened liver disease. MEGX values were related both to the histological score in chronic hepatitis and to the clinical score in cirrhosis. Significantly lower values were found in females < 50 yr of age than in males of the same age. The MEGX test showed great efficacy in discriminating between chronic hepatitis and cirrhosis compared with standard liver tests. CONCLUSIONS: Measurement of MEGX formation proved to be a safe test, allowing us to show that functional subgroups can be identified both in chronic hepatitis and in cirrhosis. Thus, this test could integrate both the histological grading of chronic hepatitis and the clinical staging of cirrhosis.

Adolescent↗
PubMed1996

Glycosylated hemoglobin and fructosamines: does their determination really reflect the glycemic control in diabetic patients?

The present experiment was designed to determine whether scavenging capacity of serum, in addition to glucose level, influences hemoglobin and serum protein glycosylation in non-insulin dependent diabetic patients. For this purpose forty-seven patients homogeneous for age, disease duration, therapy and glyco-metabolic control were selected. Fasting and post-prandial glycemia and insulinemia as well as glycosuria were weekly analysed during the sixty days preceding glycosylated hemoglobin (HbA1c), fructosamines and serum scavenging capacity determination. This last parameter has been evaluated by a method based on the property of beta-phycoerythrin (beta-PE) to loss its fluorescence when damaged by oxygen radicals, that were produced by Cu++ and H2O2. The oxygen radical absorbance capacity (ORACOH) of serum was assayed as the ability of serum to delay the loss of beta-PE fluorescence. As expected, a statistically significant positive correlation was found comparing both fructosamines and HbA1c levels with mean fasting glycemia measured over twenty and sixty days, respectively. The key result of this study is represented by the finding that both HbAlc and fructosamines levels show a statistically significant negative correlation with ORACOH values. This correlation can explain a large percent of the data dispersion occurring when ORACOH is not taken into account. In order to better describe the role of ORACOH, patients were separated into two sub-groups with an ORACOH lower (L-ORACOH) and greater (H-ORACOH) than 100 U/ml. Examining the correlation between mean fasting glycemia and the two glycosylated proteins considered in these two sub-groups, curves with different slopes were obtained, supporting that the rate of glycosylation of both proteins was higher in L-ORACOH patients as compared to those with H-ORACOH. Present data suggest that for a proper interpretation of the HbA1c and fructosamines data in diabetic patients, the scavenging capacity level of serum should be taken into account.

Aged↗
PubMed1996

Relationship between plasminogen activator inhibitor type-1 plasma levels and the lipoprotein(a) concentrations in non-insulin-dependent diabetes mellitus.

The first part of the paper deals with the relationship between two inhibiting factors of the complex enzyme cascade regulating fibrinolysis, namely plasminogen activator inhibitor type-1 (PAI-1) and lipoprotein(a) (Lp(a)). Blood concentrations of Lp(a), PAI-1 antigen (PAI-1 AG) and activity (PAI-1 AT), and the main parameters of lipo- and glyco-metabolic balance were studied in 80 type II diabetic patients. Roughly hyperbolic patterns have been found between PAI-1 and Lp(a). Negative statistically significant linear correlation can be elicited when Log PAI-1 AG and Log PAI-1 AT values are plotted versus Lp(a) values, the first one being particularly tight. These findings suggest a nearly on/off control of the two parameters, limiting the risk of hypofibrinolysis. The second part of the paper was aimed at verifying this hypothesis. A group of 30 diabetic patients were treated for 3 months with metformin, an antidiabetic biguanide compound which has been reported to reduce PAI-1 levels both in diabetic and in non-diabetic patients. Metformin significantly reduced PAI-1 AG and PAI-1 AT but did not influence plasma Lp(a) levels. A clear linear correlation between the basal Lp(a) values and the changes in PAI-1 AG levels was found. An even tighter correlation was elicited between the decrease in PAI-1, and PAI-1 pretreatment values.

Aged↗
PubMed1996

Morphological bases for thallium-201 uptake in cardiac imaging and correlates with myocardial blood flow distribution.

To determine the morphological bases of thallium-201 myocardial distribution in chronic cardiac dysfunction and their relation to myocardial blood flow, myocardial slices from ten excised hearts of five chronic ischaemic heart disease patients and five idiopathic dilated cardiomyopathy patients, were imaged on a gamma camera to quantitate the uptake of thallium-201, injected 4 h before surgery, and myocardial blood flow from distribution of technetium-99m-labelled human albumin microspheres injected during surgery. Tracer distribution was correlated with histologically assessed myocardial fibrosis and myocytolysis. Thallium-201 uptake was inversely related to fibrosis (r = -0.73, in ischaemic heart disease, r = -0.65 in idiopathic dilated cardiomyopathy). In ischaemic heart disease, myocardial blood flow was related neither to thallium-201 uptake (r = 0.41) nor to the extent of fibrosis (r = -0.48). In this group, segments with normal or mildly reduced thallium-201 uptake showed significantly lower fibrosis than those with moderate or severe uptake defects (5 +/- 7% and 7 +/- 11% vs 33 +/- 14% and 42 +/- 12%, respectively, P < 0.0001. In a clinical model of chronic ischaemic dysfunction, despite severely depressed myocardial blood flow, extensive areas of myocardium devoid of significant structural impairment are present. Thallium-201 uptake effectively discriminates regions with preserved viability from those with relevant myocardial damage.

Adult↗
PubMed1996

Effect of the new calcium antagonist lercanidipine and its enantiomers on the migration and proliferation of arterial myocytes.

The in vitro effects were investigated of the new dihydropyridine calcium antagonist (CA) lercanidipine and its enantiomers on arterial myocyte (smooth muscle cell; SMC) migration and proliferation as related to L-type calcium channel inhibition. Lercanidipine and its enantiomers inhibited the replication and migration of arterial myocytes in concentration ranging from 10 to 50 microM. The antiproliferative effect of lercanidipine, evaluated as cell number, was dose dependent, with a potency similar to that of lacidipine and nifedipine, and was unrelated to the stereoselectivity of enantiomers to bind L-type calcium channels. The cell doubling time increased with drug concentration < or = 122 versus 38 h for controls. The cell growth inhibition induced by lercanidipine and its enantiomers was reversible. Lercanidipine dose dependently decreased [3H]thymidine incorporation into DNA; the (R)-enantiomer, displaying the lowest CA activity, was the most potent in this respect. The tested compounds were able to inhibit fibrinogen-induced myocyte migration in a dose-dependent manner, with the (R)-enantiomer showing the more pronounced effect. To directly rule out the role of calcium channels in the antiatherosclerotic properties of lercanidipine, we examined the effect of the compounds on serum-stimulated calcium influx in SMC. Fluorimetry of Fluo 3 was used to measure changes in free cytosolic Ca2+ concentration ([Ca2+]i) in SMC after long-term preincubation (24 h) with the tested CA. Lercanidipine and its enantiomers (25 microM) decreased the serum-induced elevation of [Ca2+]i in SMC with the (S)-enantiomer (69% inhibition) 2.4-fold more active than the counterpart and the racemate (29% inhibition). In conclusion, our in vitro results suggest that lercanidipine may directly interfere with events involved in atherogenesis. The studies performed with enantiomers of lercanidipine suggest that the observed effects are not related to the blockade of voltage-dependent Ca2+ channels and confirm at least in vitro a pharmacologic potential of the compound to negatively influence the process of atherogenesis.

Animals↗
PubMed1996

Functional antagonistic activity of Rec 15/2739, a novel alpha-1 antagonist selective for the lower urinary tract, on noradrenaline-induced contraction of human prostate and mesenteric artery.

The aim of this study was to compare with known reference standards the functional in vitro alpha-1 antagonistic activity of Rec 15/2739 on noradrenaline-induced contractions of human prostate and mesenteric artery. We also characterized these tissues with regard to the alpha-1 adrenoceptor subtypes present. Comparing the apparent pKB values revealed Rec 15/2739 to be one of the most potent compounds action on the prostate. Its potency was slightly lower than that of tamsulosin and was higher than the potencies of prazosin, terazosin and 5-methylurapidil. On the mesenteric artery, tamsulosin was the most potent compound. Comparing the results from the functional studies with those obtained from radioreceptor binding studies, we found that the potency (pKB value) in inhibiting the contraction of prostatic tissue showed a close and significant correlation with the affinity for native and recombinant alpha-1A adrenoceptors. No significant correlation was found with affinity for either the native or the recombinant alpha-1B adrenoceptor subtype, or for recombinant alpha-1d receptors. Similar results were obtained for mesenteric artery. In order to characterize further the alpha-1 adrenoceptor subtypes present in the examined tissues, we investigated the functional effects of chloroethylclonidine, an alpha-1B-D subtypes selective alpha-1 adrenoceptor irreversible antagonist, and those of nifedipine, which antagonizes the extracellular calcium influx primarily mediated by alpha-1A adrenoceptor stimulation. The results indicate the presence of both chloroethylclonidine-sensitive and -insensitive alpha-1 adrenoceptor subtypes in the human prostate, whereas in mesenteric artery the alpha-1A subtype seems to be present exclusively. The possibility that the functionally relevant alpha-1 adrenoceptor subtype could be classified as alpha-1L in both tissues shoul also be considered.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1996

Antihypertensive effects of lercanidipine in experimental hypertensive rats and dogs.

The antihypertensive action of lercanidipine (CAS 132866-11-6, Rec 15/2375), a new 1,4-dihydropyridine (1,4-DHP) calcium entry blocker (CEB), was examined in spontaneously hypertensive rats (SHR) and renal hypertensive dogs after acute and repeated administration, in comparison to several reference 1,4-DHPs. In acute experiments in SHR, lercanidipine reduced diastolic blood pressure showing a potency similar to felodipine and 2-3 fold higher than those of nicardipine and nitrendipine, after both intravenous and oral administration. Analysis of the area under the curves of percent reduction of diastolic blood pressure exerted for 3 and 8 h after intravenous and oral administrations, respectively, showed that the duration of the antihypertensive effect of lercanidipine was longer than that of the reference dihydropyridines. After repeated administrations to SHR no tachyphylaxis was observed, as indicated by the marked and persistent decrease in systolic blood pressure elicited by lercanidipine, given orally once a day for 21 days. Moreover, starting from the first week of treatment, the daily basal values of systolic blood pressure of the rats treated with lercanidipine were significantly lower than those of the placebo-treated group. In renal hypertensive dogs, after acute oral administration, lercanidipine was as potent as nitrendipine. After repeated administration, the action of lercanidipine was longer lasting than that of nicardipine and no decrease in the antihypertensive effects was observed. The in vivo studies show that lercanidipine has a potent and long-lasting antihypertensive profile, suggesting that this compound may be used for once-a-day treatment.

Administration, Oral↗