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Biomedical subjects

A Rappelli

Publications and source records attributed to A Rappelli.

At least 19 recordsLinked to original sources
PubMed2006

Expression of potassium channel isoforms mRNA in normal human adrenals and aldosterone-secreting adenomas.

Increased aldosterone secretion has been found in a mouse lacking the KCNE1 gene which codes for a regulatory protein of the KCNQ1 gene product, forming the channel for the outward rectifying delayed K+ current. Abnormalities in proteins regulating the K+ fluxes across membranes may be responsible for aldosterone-secreting adenomas (aldosteronomas) also because K+ channels are involved in cell growth. Normal and adenomatous adrenal samples and NCI-H295 cell line were used to: a) evaluate KCNE1 and KCNQ1 gene expression, b) sequence the full length cDNAs of KCNE1 and both KCNQ1 isoforms. These differently spliced KCNE1 and KCNQ1 mRNAs were expressed in adrenal tissue. In contrast, KCNQ1 isoform 2 mRNA was not expressed in kidney control tissues and NCl-H295 cell line. NCI-H295 cell line also had a significantly lower expression of KCNQ1 isoform 1 mRNA than normal adrenals and aldosteronomas. We did not find any somatic mutations in the coding sequences of both genes. This different expression pattern of KCNQ1 isoforms in NCI-H295 cell line with the lack of the mRNA for the dominant-negative KCNQ1 isoform 2 supports the involvement of voltage-gated K+ channel in cell proliferation.

Adenoma↗
PubMed2004

Cardiovascular effects of sildenafil in hypertensive men with erectile dysfunction and different alleles of the type 5 cGMP-specific phosphodiesterase (PDE5).

Erectile dysfunction (ED) is frequent in patients with essential hypertension (EH); a likely common pathogenetic pathway could be a reduced ability of arteriolar vascular smooth muscle (VSM) to relax. Increasing intracellular levels of cGMP reduce the contractile status of VSM; on the contrary, type 5 cGMP-specific phosphodiesterase (PDE5, codified by PDE5A gene) regulates cGMP levels through its clearance. The PDE5A gene represents a good candidate for the intermediate phenotype EH/ED: genetic variants of the PDE5A may predispose to EH and ED and could affect the local and systemic response to sildenafil administration. Thus, a functionally relevant portion of PDE5 5'-flanking promoter region was analyzed by PCR and direct sequencing in patients with EH and idiopathic ED. The sequences obtained showed a T/G polymorphism at position -1142, near an AP1 regulatory element, that was not apparently associated with the intermediate phenotype. We also studied the relationship between this polymorphism and the effects of oral sildenafil on blood pressure (BP) and heart rate (HR) in men with ED. Sildenafil caused a significant decrease of BP, but had no effects on HR; statistical analysis showed no differences in BP and HR variations among PDE5A genotypes. In conclusion, our data showed no correlations of a novel polymorphism of the PDE5A promoter gene with the intermediate phenotype EH/ED and the BP and HR response to sildenafil administration. Further studies are necessary to define the role of this polymorphism and to study the genetic predisposition for EH with ED.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Role of the natriuretic peptide system in lipogenesis/lipolysis.

AIM: There is recent evidence that the natriuretic peptide (NP) system promotes adipose tissue lipolysis in primates. This effect is mediated by the interaction of NP with its active receptors through guanylyl cyclase activation and cGMP production. This review will briefly focus on the new aspects of NP pathophysiology in man. DATA SYNTHESIS: NP receptors have been described in rodent adipocytes, and the expression of their mRNA is found in human adipose tissue together with high level of ANP binding sites. In isolated fat cells, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were able to stimulate lipolysis as much as isoproterenol, a non-selective beta-adrenergic receptor agonist, whereas C-type natriuretic peptide (CNP) had the lowest lipolytic effect. The potent lipolytic effect of NP has also been confirmed in samples of abdominal adipose tissue from healthy subjects. The potency order of the lipolytic effect (ANP > BNP > CNP) and ANP-induced cGMP production supported the presence of type A natriuretic peptide receptor in human fat cells. The effect of NP on lipid metabolism is confirmed by the fact that intravenous ANP infusion is followed by plasma NEFA and glycerol concentration increase (reflecting lipid mobilisation). CONCLUSIONS: The NP system seems to play an important role in lipid metabolism, possibly affecting the pathophysiology of obesity and obesity-related disorders, such hypertension. Further studies, however, are needed to completely establish the mechanisms involved in NP-induced lipolysis and the real relevance of this new pathway specific of primates.

Humans↗
PubMed2003

Aldosterone synthase alleles and cardiovascular phenotype in young adults.

The C(-344)T promoter polymorphism of the human aldosterone synthase (CYP11B2) gene has been associated with hypertension and cardiac hypertrophy, but there were contrasting data. We analysed the genotype/phenotype associations between this polymorphism and cardiovascular variables in a young adult population, where interactions among genes, gene-environment, and acquired ageing-related organ damage are reduced. Anthropometric measurements, blood pressure, heart rate, left ventricular variables (by echocardiography), and carotid artery wall intimal-media thickness (by high-resolution sonography and digitalized morphometry) were taken in 420 white Caucasian students (mean age 23.5 years, s.d. 2.5 years). CYP11B2 alleles were detected by genomic polymerase chain reaction followed by digestion. Taking into account the three possible models of inheritance, we found no differences in the considered variables, except for an independent effect of the C(-344) allele on SBP in males (TT 125.6 (1.6), TC 128.4 (1.2) and CC 130.5 (2.2), mmHg, media (ES), P=0.03), and on interventricular septum thickness in diastole in females (CC 6.98 (0.12) vs TT 6.87 (0.09) and TC 6.87 (0.07), mmHg, P<0.01), in the codominant model. In conclusion, the CYP11B2 C(-344)T polymorphism appears to have a slight role in the cardiovascular phenotype of young healthy adults, even if these genotype/phenotype relationships might change with ageing.

Adult↗
PubMed2003

Absence of somatic mutations in natriuretic peptide receptor type A gene in human aldosterone-secreting adenomas.

Somatic mutations of genes codifying for key regulatory proteins are the cause of different types of hormone-secreting adenomas. Natriuretic peptides (NP) are the strongest inhibitors of aldosterone secretion but aldosterone-secreting adenomas (aldosteronomas) are resistant to this inhibition and have reduced binding sites for NPs. The objective of this study was to sequence the entire coding region of the NP receptor type A (NPRA, codified by the Npr1 gene) to find loss-of-function somatic mutations. Total RNA was extracted from eight aldosteronomas and cDNA was synthesized. NPRA mRNA expression was evaluated by Northern blot analysis and compared with beta-actin mRNA as the housekeeping gene. Twelve primer couples were designed on the basis of the Npr1 gene organization to amplify, by PCR, all 22 coding exons of the gene. The two strands of amplified DNAs were purified and directly sequenced by automated capillary sequencer. NPRA mRNA expression did not differ among aldosteronomas. Npr1 open reading frame sequences obtained from eight aldosteronomas did not contain any mutation. The coding sequences of all 22 exons were identical in all samples and identical to published sequences. In the 3'-untranslated region (3'-UTR) a new length difference 3C/4C polymorphism was found at position 15 129 (three adenomas were 3C/4C and two were 3C/3C). Such a 3C/4C polymorphism was present in genomic DNA from 80 control subjects (25, 4C/4C; 40, 3C/4C; 15, 3C/3C). Mutations in the coding exons of the Npr1 gene do not appear to be a common cause of aldosteronomas. Moreover, the exons of Npr1 encoding for the translated portion of mRNA do not appear to be prone to polymorphisms. The polymorphism identified in the 3'-UTR might affect mRNA stability resulting in lower receptor synthesis, but it is not likely to confer a predisposition to the development of aldosteronomas.

Adenoma↗
PubMed2001

Cardiovascular phenotype of young adults and angiotensinogen alleles.

OBJECTIVES AND DESIGN: Angiotensinogen (AGT) gene variants influence angiotensinogen plasma levels in children and young adults. The angiotensinogen promoter (-6)A variant facilitates gene transcription in human tissues and it has been associated with high blood pressure in older adults. A young adult population can be used as a model to study genotype/phenotype associations between AGT (-6) variants and cardiovascular variables. METHODS AND RESULTS: Anthropometric measurements, blood pressure and heart rate were taken in 422 white Caucasian students (mean age 23.5 years, SD 2.5 years). Family history for hypertension, physical activity and smoking history were evaluated. Left ventricular variables were measured by echocardiography. Carotid artery wall intimal-media thickness (IMT) was measured by high resolution sonography and digitalized morphometry. The AGT G(-6)A alleles were evaluated by mutagenically separated polymerase chain reaction controlled by direct sequencing. No significant associations were found between angiotensinogen genotype and blood pressure, cardiac variables [except for deceleration time in females which increased with the number of (-6)A alleles] and IMT. Allele frequencies were similar between the first and third tertile of blood pressure and left ventricular mass, and were also similar between negative or positive family history for hypertension (the last group having significantly higher systolic blood pressure in males, P = 0.04 and diastolic blood pressure in females, P < 0.01). Moreover, no relevant interaction on the cardiovascular variables was found between AGT genotype and body mass index. CONCLUSIONS: The angiotensinogen G(-6)A variants do not affect cardiovascular parameters in young adults, but an effect of this polymorphism on cardiovascular phenotype (and hypertension) in older adults cannot be excluded. Additional factors, associated with ageing, should be present to unleash the supposed unfavourable potential of the (-6)A angiotensinogen variant.

Adult↗
PubMed2000

Patterns of hypertension management in Italy: results of a pharmacoepidemiological survey on antihypertensive therapy. Scientific Committee of the Italian Pharmacoepidemiological Survey on Antihypertensive Therapy.

OBJECTIVE: To collect statistically significant information on patterns of antihypertensive therapy in medical practice, with particular attention to the drugs used in the pharmacological management of hypertensive patients and the reasons for the limited achievement of therapeutic goals during treatment DESIGN: A survey conducted among general practitioners, specialists, and hypertensive patients. METHODS: A total of 28,000 physicians were contacted by letter and 3,394 declared their willingness to participate and received a questionnaire. Subsequently, 1,255 questionnaires suitable for analysis (corresponding to 37.0% of adhering physicians) were received. In addition, 4,612 questionnaires completed by patients were pooled and evaluated. The prevalence of hypertension was calculated from a base of 254,192 patients, seen by general practitioners. RESULTS: The prevalence of hypertension, defined as systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg, or current treatment, was 19.7%. The average number of hypertensive patients in each general practitioner's file, covering the previous 12 months, was approximately 230. Physicians reported a 66% rate of discontinuation of treatment or switching to another drug. Physicians and patients both considered inadequate blood pressure control and side effects to be the two main reasons for switching antihypertensive therapy, but in opposite order. Furthermore, physicians indicated a prevalence of drug side effects between 10 and 20%, according to class of drug used, whereas 69% of patients reported to have experienced side effects. In the doctors' opinions, there were many reasons for poor patient adherence: complexity of the drug regimen, appearance of side effects, forgetfulness, reduced patient understanding of the need for long-term continuation of treatment, and refusal to accept a chronic pathological condition. CONCLUSIONS: The survey showed awareness of the disease among physicians and provides a representation of the experiences of both general practitioners and specialists, in addition to that of their patients. During antihypertensive therapy, a disconcerting degree of discontinuation and switching of drugs occurred. Insufficient blood pressure control and side effects accounted for most of the observed treatment changes. This survey revealed the existence of a gap between the physicians' perception of tolerability and the real experience of patients, a clear need for greater tolerability of treatments, and a need for an enhancement of patient-physician communication.

Antihypertensive Agents↗
PubMed1999

A novel promoter variant of the natriuretic peptide clearance receptor gene is associated with lower atrial natriuretic peptide and higher blood pressure in obese hypertensives.

OBJECTIVE AND DESIGN: The clearance receptor for natriuretic peptides (NPRC), a candidate gene for essential hypertension, is highly expressed in adipose tissue, where is nutritionally regulated. The objectives of the present study were to sequence the human 5'-flanking regulatory region of NPRC, to identify allelic variants and their frequencies, and to study the genotype/phenotype correlation in hypertensive patients. METHODS AND RESULTS: Using polymerase chain reaction (PCR) and direct automated sequencing, a biallelic (A/C) polymorphism was detected at position -55 in a conserved promoter element named P1. The novel C(-55) variant makes the promoter sequence identical to the mouse gene and introduces a second Hgal site in the amplified DNA, allowing the genotyping of a large number of subjects. In a random sample of 232 white Caucasians the C(-55) allele was more commonly found (81.7% of all alleles) with 155 CC (66.8%), 69 AC (29.7%) and only eight AA (3.5%) genotypes. Atrial natriuretic peptide (ANP) levels were determined in 84 patients with essential hypertension. In the presence of obesity (body mass index (BMI) > or = 30 kg/m2) the homozygous CC hypertensives (n = 21) had significantly lower plasma ANP (33.6 +/- 11.1 pg/ml) compared with the AC patients (n = 11; 46.8 +/- 15.9 pg/ml; P = 0.01), whereas systolic blood pressure (SBP) and mean blood pressure (MBP) had the opposite association (SBP 163.9 +/- 18.7 versus 150.9 +/- 12.9 and MBP 123.3 +/- 12 versus 114.5 +/- 5.9 mmHg; P< 0.05). The difference in ANP levels were also present when overweight patients (BMI > or = 27 kg/m2) were considered. CONCLUSION: A common 'ancestral' C(-55) variant of the NPRC P1 promoter is associated with lower ANP levels and higher SBP and MBP in obese hypertensives. The C(-55) variant, in the presence of increased adiposity, might reduce plasma ANP through increased NPRC-mediated ANP clearance, contributing to higher blood pressure.

Adult↗
PubMed1999

Low calorie diet enhances renal, hemodynamic, and humoral effects of exogenous atrial natriuretic peptide in obese hypertensives.

The expression of the natriuretic peptide clearance receptor is abundant in human and rat adipose tissue, where it is specifically inhibited by fasting. In obese hypertensives, plasma atrial natriuretic peptide (ANP) levels were found to be lower than in obese normotensives. Therefore, the increased adipose mass might influence ANP levels and/or its biological activity. The aim of the present study was to evaluate whether the humoral, hemodynamic, and renal effects of exogenous ANP in obese hypertensives might be enhanced by a very low calorie diet. Eight obese hypertensives received a bolus injection of ANP (0.6 mg/kg) after 2 weeks of a normal calorie/normal sodium diet, and blood pressure (BP), heart rate, ANP, cGMP, plasma renin activity, and aldosterone were evaluated for 2 hours before and after the injection. Diuresis and natriuresis were measured every 30 minutes. The patients then started a low calorie/normal sodium diet (510 kcal/150 mmol/d) for 4 days, and then the ANP injection protocol was repeated. The low calorie diet induced a slight weight loss (from 90.6+/-1.1 to 87. 7+/-1.2 kg; P<0.01), which was accompanied by increase of cGMP excretion (from 146.0+/-10.1 to 154.5+/-9.5 nmol/24 h; P<0.05) together with a reduction of BP (P<0.01 versus basal levels). ANP injection after diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis, and natriuresis increased significantly only after diet. Similarly, the decrease of BP after ANP administration was significantly higher after diet (change in mean arterial pressure, -6.4+/-0.7 versus -4. 0+/-0.6 mm Hg; P<0.05) as well as that of aldosterone (P<0.01). These data show that a low calorie diet enhances the humoral, renal, and hemodynamic effects of ANP in obese hypertensives and confirm the importance of caloric intake in modulating the biological activity of ANP, suggesting that the natriuretic peptide system can play a role in the acute changes of natriuresis and diuresis associated with caloric restriction.

Aldosterone↗
PubMed1998

Reproducibility and clinical value of the trough-to-peak ratio of the antihypertensive effect: evidence from the sample study.

The objectives of our study were to assess the reproducibility of the trough-to-peak ratio (T/P) and to see whether a high T/P is accompanied by more organ protection or vice versa. The study included 175 (mean+/-SD age, 51+/-9 years) subjects with mild-moderate essential hypertension who had echocardiographic evidence of left ventricular (LV) hypertrophy taken from the SAMPLE study (Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation), an open-label multicenter study. The study included a 3-week washout pretreatment period, a 12-month treatment period with lisinopril (n=84) or lisinopril plus hydrochlorothiazide (n=91) once daily, and a 4-week placebo follow-up period. Results of 24-hour ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index (LVMI) were obtained before and after 3 and 12 months of treatment. T/Ps were computed in each patient by dividing the systolic and diastolic blood pressure changes at trough (changes in the last 2 hours of the monitoring period) by those at peak (average of the 2 adjacent hours with the maximal blood pressure reduction between the 2nd and 8th hour from drug intake) after 3 and 12 months of treatment. Average 24-hour blood pressure was similarly reduced at 3 and 12 months. Trough blood pressure changes at 3 and 12 months were closely correlated, as were the corresponding peak blood pressure changes. However, the 3- and 12-month T/Ps correlated to a lesser degree (r<0.42). Furthermore, the reduction of LVMI induced by treatment was similarly correlated with the treatment-induced reduction in 24-hour average, trough, and peak blood pressures but not with the T/Ps. This was also evident when the contribution to LV hypertrophy regression by 24-hour blood pressure changes and T/Ps was assessed in a multivariate regression analysis. In patients with a T/P >/=0.5 or <0.5, the regression of LVMI was similar. In conclusion, peak and trough blood pressure changes are reproducible and predict the regression of LVMI induced by treatment as well as average 24-hour blood pressure. T/Ps are less reproducible, and their value does not predict regression of organ damage by antihypertensive treatment.

Adult↗
PubMed1997

Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy. SAMPLE Study Group. Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation.

BACKGROUND: In cross-sectional studies, ambulatory blood pressure (ABP) correlates more closely than clinic BP with the organ damage of hypertension. Whether ABP predicts development or regression of organ damage over time better than clinic BP, however, is unknown. METHODS AND RESULTS: In 206 essential hypertensive subjects with left ventricular hypertrophy (LVH), we measured clinic supine BP, 24-hour ABP, and left ventricular mass index (LVMI, echocardiography) before and after 12 months of treatment with lisinopril (20 mg UID) without or with hydrochlorothiazide (12.5 or 25 mg UID). Measurements included random-zero, clinic orthostatic, and home BP. In all, 184 subjects completed the 12-month treatment period. Before treatment, clinic supine BP was 165 +/- 15/105 +/- 5 mm Hg (systolic/diastolic), 24-hour average BP was 149 +/- 16/95 +/- 11 mm Hg, and LVMI was 158 +/- 32 g/m2. At the end of treatment, they were 139 +/- 12/87 +/- 7 mm Hg, 131 +/- 12/83 +/- 10 mm Hg, and 133 +/- 26 g/m2, respectively (P < .01 for all). Before treatment, LVMI did not correlate with clinic BP, but it showed a correlation with systolic and diastolic 24-hour average BP (r = .34/.27, P < .01). The LVMI reduction was not related to the reduction in clinic BP, but it was related to the reduction in 24-hour average BP (r = .42/.38, P < .01). Treatment-induced changes in average daytime and nighttime BPs correlated with LVMI changes as strongly as 24-hour BP changes. No substantial advantage over clinic supine BP was shown by clinic orthostatic, random-zero, and home BP. CONCLUSIONS: In hypertensive subjects with LVH, regression of LVH was predicted much more closely by treatment-induced changes in ABP than in the clinic BP. This provides the first longitudinally controlled evidence that ABP may be clinically superior to traditional BP measurements.

Adult↗
PubMed1997

Plasma atrial natriuretic peptide and natriuretic peptide receptor gene expression in adipose tissue of normotensive and hypertensive obese patients.

OBJECTIVE: Human and rat adipose tissue contain very high levels of natriuretic peptides clearance receptor messenger (m)RNA, and fasting inhibits its gene expression in adipose tissue. In this study we evaluated plasma atrial natriuretic peptide (ANP) and gene expression of biologically active type A natriuretic peptide receptor (NPr-A) and clearance natriuretic peptide receptor (NPr-C) in adipose tissue of obese hypertensive and obese normotensive patients. DESIGN AND METHODS: We studied 27 untreated obese hypertensives, 26 obese normotensives (body mass index > or = 30 kg/m2), 24 non-obese essential hypertensives and 23 lean healthy subjects (body mass index < or = 25 kg/m2). Blood samples were withdrawn for ANP, plasma renin activity and aldosterone radioimmunoassays. Subcutaneous peri-umbilical adipose tissue samples were obtained, by needle aspiration, in 13 obese hypertensives and in 12 obese normotensives and used for RNA extraction. Then, complementary synthesis and semiquantitative polymerase chain reaction (PCR) with primers complementary to sequences of different exons of the genes encoding for NPr-A, NPr-C and beta-actin, were performed. 32P-labeled PCR products were separated by electrophoresis, blotted onto nylon membranes, and the exposed autoradiographic films were analysed by densitometry. NPr signals were normalized by the beta-actin expression level. RESULTS: Plasma ANP was lower in obese hypertensives than in obese normotensives (37.5+/-7 versus 43.2+/-6 pg/ml, P< 0.05), but was higher in non-obese hypertensives than in non-obese normotensives. In contrast, plasma renin activity and aldosterone were higher in the obese hypertensives. Although NPr-A and NPr-C expression were not statistically different between the two obese groups, the NPr-A: NPr-C mRNA ratios were significantly lower in obese hypertensives (P < 0.03). CONCLUSIONS: Our data suggest that in obese hypertensives compared to obese normotensives, the lower NPr-A: NPr-C ratio might determine decreased biological activity and/or an increased clearance of natriuretic peptide in adipose tissue, suggesting that the natriuretic peptide and its receptor system may be important in obesity-related hypertension where ANP levels are lower.

Actins↗
PubMed1996

Expression of natriuretic peptide receptors in human adipose and other tissues.

To characterize natriuretic peptide receptor (NPr) gene expression in human tissues, we cloned portions of the cDNAs codifying for NPr with guanylyl cyclase activity (NPr-A and NPr-B) and without guanylyl cyclase activity (NPr-C). Total RNA was extracted from samples taken at surgery from normal human tissues. NPr-A and NPr-B cDNAs obtained from lung as well as NPr-C cDNA obtained from renal cortex were cloned, characterized, and used for comparative Northern analysis. NPr-A mRNA (approximately 4 kb) was most abundant in adipose tissue (8 patients) independently on the site of sampling, whereas it was approximately 2.5-fold and 5-fold less abundant, respectively, in kidney (either renal cortex or papilla from 3 patients) and adrenal (4 patients), known target tissues of natriuretic peptides. NPr-C mRNAs (approximately 7.7 and 6.8 kb) had a similar tissue distribution but the highest levels were found in renal tissue and only very low expression levels were found in adrenals (approximately 20-fold lower than renal cortex). The ratio of NPrA versus NPr-C mRNA levels were highest in adrenal and lowest in renal tissue. NPr-B mRNA (approximately 4 kb), which encodes the receptor for the C-type natriuretic peptide, had a different and wide tissue distribution, including expression in ileum and liver, with the highest levels in venous and prostatic tissue. These results indicate that, in humans, different patterns of NPr expression with different NPr-A/NPr-C mRNA level ratios, are present in known target tissues of natriuretic peptides. "Non-classic" target tissues, such as the adipose one, maximally expressed NPr-A and also NPr-C, suggesting that natriuretic peptides may have wider functional activities than those previously demonstrated.

Adipose Tissue↗
PubMed1996

Angiotensin II and the adrenal.

1. Angiotensin II (AngII) evokes a variety of physiological responses in the adrenal gland. It is the major regulator of aldosterone secretion, in the medulla it enhances catecholamine release and it exerts trophic effects in the adrenal and stimulates growth factor secretion. 2. Angiotensin II acts via binding to specific receptors, located on the plasma membrane. Two pharmacologically distinct AngII receptor subtypes, type 1 (AT1) and type 2 (AT2) receptors, have been identified using the non-peptide antagonists Dup753 and PD 123177, respectively, and cDNA encoding each type have been identified. 3. In the adrenal, the AT1 receptor modulates all the known biological effects of AngII. The expression of the AT1 receptor is modulated at the mRNA and protein levels by many factors: conditions that increase levels of AngII (low sodium diet, renovascular hypertension, AngII infusion) up-regulate AT1 receptor mRNA levels and binding and increase aldosterone secretion. 4. A tissue renin-angiotensin system has been found in the adrenal, suggesting an important paracrine role for AngII in aldosterone regulation. 5. The possible involvement of AT1 receptors in human disease has been investigated by examining the role of AngII receptors in adrenal tumours. Binding and gene expression studies have shown that AngII receptors are abundantly expressed in aldosterone-producing adenoma (APA). 6. Densitometric analysis of AT1 expression in APA showed no significant differences compared with normal and non-tumorous adrenal. In addition, no mutations in the coding sequence of the AT1 receptor have been found to date in adrenal tumours.

Adenoma↗
PubMed1995

Fasting inhibits natriuretic peptides clearance receptor expression in rat adipose tissue.

OBJECTIVE AND DESIGN: The early phase of weight loss induced by fasting is associated with diuresis, natriuresis and reduction in blood pressure through unclear mechanisms. Atrial natriuretic peptide (ANP) is a cardiac hormone with potent natriuretic, diuretic and hypotensive effects mediated by 'biologically active' receptors (NPr-A). A second type of receptor mediates the clearance of ANP (the clearance receptor, NPr-C). Since NPr-C appears to be abundant in adipose tissue, we analysed NPr-C and NPr-A gene expression in white and brown adipose tissue (WAT and BAT) as well as in renal cortex of fasting rats. Plasma ANP, cyclic GMP and aldosterone were also measured. METHODS: Twelve male Wistar rats were deprived of food for about 50 h, and 12 other rats were fed ad libitum. Periepididymal WAT, interscapular BAT and left renal cortex were used for RNA extraction and northern blot analysis with rat NPr-C and NPr-A complementary DNA probes labelled with 32P-dCTP. Densitometric analysis of hybridization signals was corrected by beta actin expression before statistical analysis. Blood was drawn for ANP, cyclic GMP (cGMP) and aldosterone radioimmunoassays, which were also measured in a group of six rats deprived of food for 25 h. RESULTS: A dramatic decrease in NPr-C steady-state messenger RNA levels was observed both in WAT (about 3.6-fold, P < 0.001) and in BAT (about threefold, P < 0.01), but fasting did not affect the expression of NPr-A in adipose tissues. In the renal cortex NPr-C and NPr-A messenger RNA levels were unaffected by fasting. ANP and aldosterone levels were reduced after fasting whereas cyclic GMP was increased at 25 h, but the differences did not reach statistical significance. CONCLUSIONS: Fasting exerts a tissue-specific and gene-specific suppression of NPr-C gene expression in adipose tissue that appears to be accompanied by an increased biological activity of ANP. The natriuresis and diuresis and reduction of blood pressure induced by fasting might result from a reduced expression of NPr-C in adipose fat pads.

Adipose Tissue↗