Biomedical subjects

M Volpe

Publications and source records attributed to M Volpe.

At least 19 recordsLinked to original sources

PubMed2002

Long-term persistence with antihypertensive drugs in new patients.

The objective of this study was to investigate stay-on-therapy patterns over 3 years among patients prescribed different classes of antihypertensive drugs for the first time. A retrospective analysis of information recorded in the drugs database of the Local Health Unit of Ravenna (Italy) was carried out on 7312 subjects receiving a first prescription for diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II antagonists between 1 January and 31 December 1997. Patients were followed up for 3 years. All prescriptions of antihypertensive drugs filled during the follow-up periods were considered. The patients continuing or discontinuing the initial treatment, the duration of treatment, and the doses taken were all calculated, as well as main factors influencing the persistence rate. The drugs prescribed were predominantly ACE-inhibitors, followed by calcium channel blockers, diuretics, beta-blockers and angiotensin II antagonists. A total of 57.9% of patients continued their initial treatment during the 3-year follow-up period, 34.5% discontinued the treatment, whilst 7.6% were restarted on a treatment in the third year. Persistence with treatment was influenced by: age of patient (persistence rate increasing proportionately with advancing years), type of drug first prescribed (persistence rate higher with angiotensin II antagonists, progressively lower with ACE-inhibitors, beta-blockers, calcium channel blockers and diuretics), gender of patient (persistence was better in males), age of general practitioner (GP) (the younger the GP, the better the persistence rate) and gender of GP (better stay-on-therapy rate with male GP prescribing). In the case of patients treated continuously, mean daily dose increased progressively over the 3 years. With adequate markers, helpful data can be collected from prescription claims databases for the purpose of monitoring the persistence of patients in continuing their medication, and the quality of antihypertensive treatment in a general practice setting.

Antihypertensive Agents↗

PubMed2001

Determinants and clinical significance of natriuretic peptides and hypertrophic cardiomyopathy.

AIMS: Atrial and brain natriuretic peptide levels closely reflect impaired left ventricular function in patients with heart failure. In the present study we assessed the determinants and the clinical significance of atrial and brain natriuretic peptide plasma levels in hypertrophic cardiomyopathy. METHODS AND RESULTS: In 44 patients with hypertrophic cardiomyopathy (40+/-15 years) we evaluated: (a) atrial and brain natriuretic peptide plasma levels; (b) left ventricular hypertrophy; (c) left ventricular ejection fraction; (d) transmitral and pulmonary venous flow velocity patterns, and left atrial fractional shortening; (e) left ventricular outflow tract gradient; (f) maximal oxygen consumption. Left ventricular hypertrophy influenced only brain natriuretic peptide levels (r=0.32;P<0.05). Atrial and brain natriuretic peptide plasma levels did not correlate with left ventricular ejection fraction, but correlated with left ventricular outflow tract gradient (r=0.35;P<0.05; and r=0.40, P=0.022, respectively) and left atrial fractional shortening (r=-0.57;P<0.001, and r=-0.35;P<0.05, respectively). Atrial but not brain natriuretic peptide plasma levels were inversely related to maximal oxygen consumption (r=-0.35;P<0.05). By stepwise multiple regression analysis, left atrial fractional shortening and left ventricular outflow tract gradient were the only predictors of atrial and brain natriuretic peptide plasma levels, respectively. CONCLUSIONS: In hypertrophic cardiomyopathy, atrial natriuretic peptide plasma levels are mainly determined by diastolic function: this explains the relationship with exercise tolerance. In contrast, brain natriuretic peptide plasma levels are mainly determined by left ventricular outflow tract gradient.

Adolescent↗

PubMed2001

The atrial natriuretic peptide: a changing view.

The atrial natriuretic peptide (ANP), a component of the natriuretic peptide family, was discovered in 1981 when de Bold and his coworkers observed a natriuretic effect induced by infusion of atrial extracts in rats. Subsequently, an impressive amount of research has been carried out in order to identify the structure of the active peptide and its receptors, to characterize the biological functions of ANP and its involvement in the pathophysiology of diseases and, finally, its direct contributory role in the pathogenesis of some cardiovascular disorders. ANP plays a key role in the regulation of salt and water balance, as well as of blood pressure homeostasis. In addition, ANP is involved in the pathophysiology of hypertension and heart failure, and exerts a cellular antiproliferative effect in the cardiovascular system. More recently, a direct contributory role of ANP in the development of hypertension and of cerebrovascular disorders has been suggested by the use of molecular genetic approaches. Therefore, our understanding of the pathophysiologic relevance of ANP has changed over time, finally leading to the identification of ANP as a potential determinant of cardiovascular diseases, rather than as a simple marker of cardiac and vascular dysfunctions. This novel view of ANP may open interesting research pathways.

Animals↗

PubMed2001

Genetic susceptibility to cerebrovascular accidents.

Cerebrovascular accidents are the third leading cause of death after myocardial infarction and cancer in all Western societies. A more complete understanding of the pathogenetic determinants of stroke is required in order to achieve a better prevention and treatment of this common disease. Recently, based on convincing epidemiological and experimental evidence, the concept of stroke as a complex, multifactorial, polygenic disease has been well assessed. Thus, together with known modifiable determinants, such as smoking, obesity, hypertension, cardiac diseases and diabetes, specific hereditary factors for stroke are now taken into account when analysing the pathogenesis of cerebrovascular accidents. In particular, there have recently been important findings related to the genetic basis of stroke in suitable animal models and in humans, thus representing the promise of a more thorough understanding of the pathogenesis of stroke in the future and of a more specific preventive and therapeutic approach to this common pathological condition.

Animals↗

PubMed2001

Endothelial dysfunction and stroke.

Endothelial dysfunction, intended as the complex multifaced pathological product of different vasculotoxic agents or injuries, is viewed today as an attractant intermediate phenotype of cardiovascular diseases with usually long and unpredictable natural history. Furthermore, endothelial dysfunction may not only represent a vascular disease marker, but may actually play an important pathogenetic role, leading to progression of the disease and unfavourable outcomes. Among these vascular diseases, cerebrovascular accidents, namely stroke, clearly represent a paradigmatic example of the potential role of dysfunctional endothelium. In fact, in the world's growing elderly population few diseases are more dreaded than stroke. With an increasing incidence and mortality of 30%, stroke carries the threat of death or long-term disability and suffering. Endothelium produces nitric oxide (NO) under basal conditions and in response to a variety of vasoactive stimuli in large cerebral arteries and in the cerebral microcirculation. In addition to exerting a tonic dilator effect on the cerebral circulation, basal release of NO may protect cerebral endothelium by inhibiting aggregation of platelets and leukocytes. In this paper, we analyse current evidence suggesting that endothelial dysfunction can play a role in the pathogenesis of ischaemic stroke.

Animals↗

PubMed2001

Differential regulation of Epstein-Barr virus (EBV) latent gene expression in Burkitt lymphoma cells infected with a recombinant EBV strain.

Epstein-Barr virus (EBV)-negative Burkitt lymphomas (BLs) can be infected in vitro with prototype EBV strains to study how the virus may affect the phenotype of tumor cells. Studies thus far have concentrated on the use of transforming B95-8 and nontransforming P3HR1 strains. Immunological and phenotypic differences between the sublines infected with these two strains were reported. The majority of these differences, if not all, can be attributed to the lack of EBNA-2 coding sequences in the P3HR1 strain. The recent development of a selectable Akata strain has opened up new possibilities for infecting epithelial and T cells as well. We infected five EBV-negative BL lines with the recombinant Akata virus. Our results indicate that the infected cell lines BL28, Ramos, and DG75 express EBNA-1, EBNA-2, and LMP1, the viral proteins associated with type III latency, and use both YUK and QUK splices. In contrast, two EBV-negative variants of Akata and Mutu when reinfected displayed restricted type I latency and expressed only EBNA-1. All clones of infected Mutu cells used the QUK splice exclusively. The usage of Qp was observed in a majority of Akata clones. Some Akata clones, however, were found to have double promoter usage (Qp and C/Wp) but at 4 months after infection did not express EBNA-2. The results demonstrate differential regulation of EBV latency in BLs with the same recombinant viral strain and suggest that the choice of latency type may be cell dependent. The restricted latency observed for infected Akata and Mutu cells indicates that a BL may opt for type I latency in the absence of immune pressure as well.

Burkitt Lymphoma↗

PubMed2001

Non-random chromosomal distribution of SSLPs: systematic assessment using a novel genetic linkage map between two closely related rat strains.

Simple sequence length polymorphisms (SSLPs) are a widely used tool for genetic studies in humans and model animals. Experimental crosses among closely related strains that differ primarily in the trait that is to be mapped carry the advantage of avoiding co-segregation of potentially confounding traits. However, their realization is encumbered by the limited availability of newly arisen informative SSLPs among such strains. Here we report the establishment of a genome-wide SSLP panel for the spontaneously hypertensive rat (SHR) and its close relative, the stroke-prone SHR (SHRSP), consisting of a total of 273 polymorphic markers that were found among 2,734 rat SSLPs screened. In addition to limitations in numbers, we also found the distribution of informative markers to be heterogeneous, with clustering and paucity of informative markers, respectively, in particular regions. Notably, the majority of regions thus identified was also seen when we examined an unrelated set of strains from the literature, indicating, on a more generic level, the presence of mutagenically more and less stable genomic regions.

Animals↗

PubMed2001

Reactive oxygen species mediate endothelium-dependent relaxations in tetrahydrobiopterin-deficient mice.

(6R)-5,6,7,8-Tetrahydro-biopterin (H(4)B) is essential for the catalytic activity of all NO synthases. The hyperphenylalaninemic mouse mutant (hph-1) displays 90% deficiency of the GTP cyclohydrolase I, the rate-limiting enzyme in H(4)B synthesis. A relative shortage of H(4)B may shift the balance between endothelial NO synthase (eNOS)-catalyzed generation of NO and reactive oxygen species. Therefore, the hph-1 mouse represents a unique model to assess the effect of chronic H(4)B deficiency on endothelial function. Aortas from 8-week-old hph-1 and wild-type mice (C57BLxCBA) were compared. H(4)B levels were determined by high-performance liquid chromatography and NO synthase activity by [(3)H]citrulline assay in homogenized tissue. Superoxide production by the chemiluminescence method was measured. Isometric tension was continuously recorded. The intracellular levels of H(4)B as well as constitutive NO synthase activity were significantly lower in hph-1 compared with wild-type mice. Systolic blood pressure was increased in hph-1 mice. However, endothelium-dependent relaxations to acetylcholine were present in both groups and abolished by inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester as well. Only in hph-1 mice were the relaxations inhibited by catalase and enhanced by superoxide dismutase. After incubation with exogenous H(4)B, the differences between the 2 groups disappeared. Our findings demonstrate that H(4)B deficiency leads to eNOS dysfunction with the formation of reactive oxygen species, which become mediators of endothelium-dependent relaxations. A decreased availability of H(4)B may favor an impaired activity of eNOS and thus contribute to the development of vascular diseases.

Acetylcholine↗

PubMed2001

Oxygen therapy, continuous positive airway pressure, or noninvasive bilevel positive pressure ventilation in the treatment of acute cardiogenic pulmonary edema.

OBJECTIVE: To compare the effects of 3 types of noninvasive respiratory support systems in the treatment of acute pulmonary edema: oxygen therapy (O2), continuous positive airway pressure, and bilevel positive pressure ventilation. METHODS: We studied prospectively 26 patients with acute pulmonary edema, who were randomized into 1 of 3 types of respiratory support groups. Age was 69+/-7 years. Ten patients were treated with oxygen, 9 with continuous positive airway pressure, and 7 with noninvasive bilevel positive pressure ventilation. All patients received medicamentous therapy according to the Advanced Cardiac Life Support protocol. Our primary aim was to assess the need for orotracheal intubation. We also assessed the following: heart and respiration rates, blood pressure, PaO2, PaCO2, and pH at beginning, and at 10 and 60 minutes after starting the protocol. RESULTS: At 10 minutes, the patients in the bilevel positive pressure ventilation group had the highest PaO2 and the lowest respiration rates; the patients in the O2 group had the highest PaCO2 and the lowest pH (p<0.05). Four patients in the O2 group, 3 patients in the continuous positive pressure group, and none in the bilevel positive pressure ventilation group were intubated (p<0.05). CONCLUSION: Noninvasive bilevel positive pressure ventilation was effective in the treatment of acute cardiogenic pulmonary edema, accelerated the recovery of vital signs and blood gas data, and avoided intubation.

Acute Disease↗

PubMed2000

Characterization of caveolae from rat heart: localization of postreceptor signal transduction molecules and their rearrangement after norepinephrine stimulation.

Caveolae are plasma membrane subcompartments that have been implicated in signal transduction. In many cellular systems, caveolae are rich in signal transduction molecules such as G proteins and receptor-associated tyrosine kinases. An important structural component of the caveolae is caveolin. Recent evidence show that among the caveolin gene family, caveolin-3 is expressed in skeletal and cardiac muscle and caveolae are present in cardiac myocyte cells. Both the ANP receptor as well as the muscarinic receptor have been localized to the caveolae of cardiac myocytes in culture. These findings prompted us to conduct a further analysis of cardiac caveolae. In order to improve our understanding of the mechanisms of signal transduction regulation in cardiac myocytes, we isolated cardiac caveolae by discontinuous sucrose density gradient centrifugation from rat ventricles and rat neonatal cardiocytes. Our analysis of caveolar content demonstrates that heterotrimeric G proteins, p21ras and receptor-associated tyrosine kinases are concentrated within these structures. We also show that adrenergic stimulation induces an increase in the amount of diverse alpha- and beta-subunits of G proteins, as well as p21ras, in both in vivo and in vitro experimental settings. Our data show that cardiac caveolae are an important site of signal transduction regulation. This finding suggests a potential role for these structures in physiological and pathological states.

Adrenergic alpha-Agonists↗

PubMed2000

Role of angiotensin II AT1 and AT2 subtype receptors in the regulation of atrial natriuretic peptide expression in salt-restricted rats.

Previous studies have suggested that angiotensin II modulates ANP secretion and this action appears to be largely independent from its hemodynamic effects. In order to explore the contribution of angiotensin II AT1 (AT1r) and AT2 (AT2r) receptor subtypes in the regulation of cardiac ANP, we studied the effects of selective antagonists of these receptors on ANP mRNA levels in the cardiac chambers of salt-restricted rats. Thirty-one Sprague-Dawley rats (12 weeks-old) weighing 250-350 g were studied during a low salt regimen and randomly assigned to the following treatment groups: AT1r-blockade (losartan) (10 mg/kg/day) (n = 18), AT2r-blockade (PD123319) (50 microg/kg/min) (n = 6), Control (salt-restriction) (n = 7). Treatments were maintained for 7 days; subsequently, 12 rats from the AT1r-blockade group were subdivided in to two groups: AT1r/AT2r-blockade (losartan +PD123319) (n = 6) and AT1r-blockade/vehicle (losartan+vehible) (n = 6), and treated for 7 additional days. Systolic blood pressure was significantly reduced by AT1r-blockade (p < 0.001), while it was not affected by AT2r-blockade. Concomitant treatment with both antagonists (AT1r/AT2r-blockade) restored blood pressure values to baseline (p < 0.001 vs. AT1r-blockade, p = n.s. vs Control). Atrial ANP mRNA was reduced by AT1r-blockade (-42%, p < 0.05) and did not change during AT1r-blockade alone. On the contrary, concomitant treatment with both antagonists resulted in a further significant inhibition of ANP expression (-65% and -36% vs Control and AT1r-blockade, respectively, both p < 0.05). ANP expression in ventricles was not affected by any of these treatments. Our results demonstrate that angiotensin II tonically modulates cardiac ANP expression in our experimental model. In particular, angiotensin II receptor subtypes AT1r and AT2r regulate atrial ANP mRNA levels through a synergic action and independently from blood pressure changes.

Angiotensin II↗

PubMed2000

Defective suppression of the aldosterone biosynthesis during stroke permissive diet in the stroke-prone phenotype of the spontaneously hypertensive rat.

Previous studies have shown that short-term high salt intake unmasks blunted plasma aldosterone suppression in stroke-prone spontaneously hypertensive rats (SHRsp). The aim of this study was to evaluate the response of aldosterone biosynthesis and production to a sustained exposure to the stroke-permissive Japanese-style diet (JD) in young stroke-prone and stroke-resistant SHRs. For this purpose, 6-week old male rats from both strains were divided into 2 dietary groups and received regular diet (SHR = 37, SHRsp = 32) or the JD and 1% saline to drink (SHR = 34, SHRsp = 30) for 4 weeks. All measurements were carried out at the end of the dietary periods. After JD, plasma aldosterone levels were significantly decreased in SHR (from 357.8 +/- 57 to 163.3 +/- 31.5 pg/ml, p < 0.05) but markedly increased in SHRsp (from 442 +/- 56.5 to 739 +/- 125.7 pg/ml, p < 0.05). Consistently, the adrenal aldosterone synthase expression was reduced by JD in SHR (p < 0.05), whereas it was even slightly raised by JD in SHRsp so that, at the end of JD, aldosterone synthase mRNA was 5-fold higher in SHRsp than in SHR. Urinary sodium excretion (mEq/24h) achieved lower levels in SHRsp, so that fractional excretion of sodium was 80.2 +/- 9% in SHR and 40.3 +/- 8% in SHRsp (p < 0.05) in balance studies performed at the end of JD. These different responses of mineralocorticoid biosynthesis and urinary sodium excretion to JD were not accounted for by different adaptations of the renin-angiotensin and atrial natriuretic peptide systems, of serum potassium levels, or of adrenal 11beta-hydroxylase expression in the two strains. Systolic blood pressure was comparable in both strains throughout the experiment. These results demonstrate enhanced aldosterone biosynthesis, associated with reduced urinary excretion of sodium in response to JD in SHRsp before the onset of stroke. This abnormality may play a role in the higher susceptibility to stroke of this model.

Aldosterone↗

PubMed2000

Etiology and pathophysiology of stroke as a complex trait.

Stroke (brain attack) is currently the third leading cause of death in Western societies. Recent advances in molecular genetics have finally demonstrated what has long been suggested by the clinical observation, that is, stroke is not only the complication of major pathologic conditions such as atherosclerosis, hypertension, or cardiac diseases, but rather it represents a complex trait itself. Thus, the pathogenesis of stroke is often the result of the combined effects of genes exerting a direct contributory role and of their interactions with several environmental determinants. A genetic dissection of stroke has been attempted in suitable animal models and in humans. With this approach, the genetic defects underlying monogenic disorders associated with stroke were identified. Moreover, important findings have recently highlighted the contribution of genes encoding cardiovascular hormones, such as the atrial natriuretic peptide, for the pathogenesis of multifactorial, polygenic forms of stroke. A more thorough understanding of the fine mechanisms, dependent from mutations within stroke susceptibility genes and underlying the disease pathogenesis, may help to introduce new specific tools to achieve better prevention and treatment of stroke.

Animals↗

PubMed2000

Analysis of the genetic basis of the endothelium-dependent impaired vasorelaxation in the stroke-prone spontaneously hypertensive rat: a candidate gene approach.

OBJECTIVE: To investigate the role of potential candidate genes in the pathogenesis of the endothelium-dependent impaired vasorelaxation that associates and co-segregates with stroke in the stroke-prone spontaneously hypertensive rat (SHRsp) compared with the stroke-resistant SHR (SHRsr). DESIGN AND METHODS: An SHRsp/SHRsr F2-intercross (n = 137; 64 males, 73 females) was obtained and, at the age of 6 weeks, it was placed under a stroke permissive Japanese-style diet for 4 weeks. At the end of the treatment the vascular function of each rat was characterized. The maximal vasorelaxation to acetylcholine after maximal vasoconstriction (delta ratio) was considered as the quantitative phenotype. The following candidate genes were related to the delta ratio: renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II AT1b receptor, atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic peptide GC-A receptor, kallikrein, endothelial nitric oxide synthase. In addition, polymorphic markers located inside areas of the rat genome where other candidates (i.e. adrenomedullin, endothelin, Ang II AT1a receptor) are known to map were included. RESULTS: The endothelial vascular dysfunction of the SHRsp showed a variable distribution among SHRsp/SHRsr F2 descendants, independently from the blood pressure levels. A genotype/phenotype co-segregation analysis for each of the genes tested did not show any statistically significant co-segregation with the vascular phenotype. CONCLUSION: A candidate gene approach used to investigate the genetic basis of the endothelial-dependent vascular dysfunction of the SHRsp strain did not reveal any evidence to support the hypothesis that the genes tested play any role in the pathogenesis of the stroke-related vascular abnormality.

Animals↗

PubMed2000

Renal implications of the renin-angiotensin-aldosterone system blockade in heart failure.

The renin-angiotensin-aldosterone system actively participates in the derangement of renal function since the early stages of heart failure (HF). A diminished capacity to excrete sodium secondary to increased proximal tubular re-absorption and loss of the renal functional reserve are the two most relevant initial alterations of renal function in which angiotensin II has been proven to act directly. Meanwhile, the octapeptide contributes to maintain glomerular filtration rate (GFR) within normal limits through efferent arteriole vasoconstriction. Administration of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor antagonists (ARA) may thus be accompanied by a functional fall in that parameter. Advanced age, higher initial serum creatinine, history of hypertension, diabetes and atrial fibrillation predict the onset of GFR impairment associated with blockade of the renin-angiotensin system. Concomitant administration of betablockers may help to protect renal function, and preliminary data indicate that the combination of ACEi and ARA is not accompanied by a higher renal risk. The good prognostic effects of aldosterone antagonists in HF does not seem to be related to intrarenal effects of these compounds with the exception of preventing potassium loss and hypokalemia. The systematic therapeutic use of drug(s) provided with beneficial renal effects, to treat arterial hypertension or myocardial ischemia, may contribute to delay of, or prevent the development of HF.

Angiotensin Receptor Antagonists↗

PubMed2000

Abnormalities of endothelial function in the pathogenesis of stroke: the importance of endothelin.

Endothelial cells play a key role in the local regulation of the vascular smooth muscle tone by producing and releasing relaxing and contracting factors. Endothelin (ET)-1, one of the most potent endogenous vasoconstrictor substances known, is produced by endothelial cells. In the cerebral vasculature ET-1 is thought to be involved in several pathological conditions, including vasospasm following subarachnoid hemorrhage and stroke. This review contains evidence suggesting that endothelial dysfunction may contribute to the development of ischemic stroke and discusses the current knowledge concerning the role of ET-1 in the pathogenesis of stroke in animal models and in humans.

Animals↗

PubMed2000

Effects of losartan treatment on cardiac autonomic control during volume loading in patients with DCM.

This study evaluated the effect of angiotensin II receptor blockade on cardiac autonomic control adaptation and urine output in response to acute isotonic volume load in patients with idiopathic dilated cardiomyopathy (DCM) and asymptomatic to mildly symptomatic heart failure. Left ventricular volumes and heart rate variability measurements were assessed at baseline and during intravenous saline load in 14 patients before and after 2 mo of losartan treatment. After losartan treatment, blood pressure values were lower, whereas left ventricular ejection fraction was higher (F = 79, P < 0.001), than before treatment. During saline load, ejection fraction decreased before losartan treatment (F = 5.6, P < 0.05) but did not change after treatment. Urinary volume, unchanged during saline load in untreated patients, increased after losartan (F = 9.38, P < 0. 001). Time-domain measurements that represent vagal modulation of heart rate (root-mean-square successive differences and percentage of differences between successive R-R intervals >50 ms) decreased during saline load in untreated patients (F = 3.1, P < 0.05 and F = 6.5, P < 0.01, respectively), but not after losartan. Similarly, a decrease in very low frequency (F = 3.2, P < 0.05), low-frequency (F = 2.9, P < 0.05), and high-frequency power (F = 6.1, P < 0.01) after saline load was observed only in untreated patients. In patients with DCM, losartan treatment improves the cardiac autonomic adaptation and increases urine output in response to volume overload.

Adult↗

PubMed2000

Angiotensin II AT2 subtype receptors: an emerging target for cardiovascular therapy.

This article reviews the impressive amount of knowledge accumulated in the last few years on the angiotensin II AT2 subtype receptor. Although still elusive, a large body of experimental evidence strongly suggests that it may play an important role in the adaptive changes of the cardiovascular structures in response to pathological conditions such as myocardial infarction, congestive heart failure or hypertension. The most intriguing aspects of the biology of this receptor, however, appear to be: 1) the regulation of its transcription, which plays an important role in the expression of the protein in adults or in injured tissues; 2) its interaction or "cross-talk" with the predominant angiotensin II receptor, the AT1 subtype, or with the receptors of other growth factors or cytokines; and 3) its connections with the bradykinin/nitric oxide pathways. These aspects may be relevant for the therapeutical use of drugs which antagonize the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, as well as for new therapeutic approaches to the treatment of cardiovascular diseases.

Angiotensin II↗