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M Mannelli

Publications and source records attributed to M Mannelli.

At least 19 recordsLinked to original sources
PubMed2002

Diagnosis and management of pheochromocytoma during pregnancy.

Although the presence of pheochromocytoma in pregnancy is extremely rare, this association deserves much attention as the tumor constitutes a very high risk for both mother and fetus. Any pregnant woman with hypertension, especially if paroxysmal or labile, or with so far unexplained "spells", should induce the clinician to consider the possibility of a pheochromocytoma. Maternal and fetal survival depend a lot on an early diagnosis, a correct medical therapy and a correct timing of delivery and surgery. In this respect, a strict collaboration between obstetricians, endocrinologists, anesthesiologists and surgeons is pivotal.

Adrenal Gland Neoplasms↗
PubMed2001

False serum calcitonin high levels using a non-competitive two-site IRMA.

Dual site antibody-base immunoassays are commonly used in clinical laboratories to quantify the CT serum concentrations as a specific and sensitive marker of medullary thyroid carcinoma (MTC). Heterophile antibodies can interfere with these assays, however, and cause erroneous results. In order to avoid this interference, immobilized and conjugated antibodies from two different animal species or immunoreactive antibody fragments, as well as the addition of non-immune globulins, are generally included among the assay reagents. We describe the case of a 73-year-old man affected by a multinodular goiter, who showed high basal CT plasma levels as measured by a monoclonal antibody based IRMA. The finding of negative results for the presence of MTC at fine needle aspiration (FNA) and the mild increase observed in plasma CT during a pentagastrin (Pg) stimulation test, suggested that the high CT levels might depend on a cross-reaction with heterophilic antibodies. In fact, after the addition of the heterophilic blocking tube (HBT) to each specimen, the CT levels markedly decreased by more than 80% (average decrease+/-SE= 87.6+/-2.668%). Such a decrease strongly suggests that in our case the routinely used F(ab')2 fragments were unable to eliminate all of the interference and that the elevated serum CT levels might have been caused by human heterophilic antibodies. In conclusion, these results indicate a novel cause of CT false positivity, suggesting that high serum CT levels, when combined with a slight increase during Pg stimulation, should be critically interpreted in view of the possible presence of heterophilic antibodies in the specimens.

Aged↗
PubMed2001

Adrenal masses in neoplastic patients: the role of laparoscopic procedure.

BACKGROUND: The incidence of complications resulting from fine-needle biopsy of adrenal masses in patients already treated by radical procedures for primitive neoplasms of the lungs and kidneys substantiates our opinion concerning laparoscopy as both a diagnostic and therapeutic procedure. METHODS: We performed 70 laparoscopic adrenalectomies from April 1995 to December 1999. In five patients, the adrenal mass appeared at follow-up evaluation in patients submitted to surgery for a spinocellular lung cancer. One patient underwent surgery for renal adenocarcinoma. In two patients, the adrenal mass was present already at the time primitive lung tumor was diagnosed, so adrenalectomy was performed at the first lung surgery in one patient and 2 weeks before lung surgery in the other patient. All the patients were placed in a lateral position for a transperitoneal approach. Right adrenal masses were present in seven patients, whereas one patient had an adrenal mass in a left location. RESULTS: No laparotomy was required. The average surgical time was 160 min. (range, 115-120 min). No morbility or mortality occurred, and the average hospital stay was 4 days (range, 3-11 days). All the patients had a complete removal of their masses, which averaged 4.5 cm (range, 2.5-6 cm) in size. Histology confirmed the metastatic origin of the mass in five of seven patients with primary lung cancer, and in one patient with previous kidney cancer. At this writing, three patients were disease free and still alive respectively at 3, 5, and 18 months. Three patients died of brain metastases respectively at 16, 36, and 36 months. An adenoma was proved in the other two cases. CONCLUSIONS: Laparoscopic adrenalectomy allows us to propose a much more aggressive approach to adrenal masses demonstrated at follow-up evaluation or in patients with primary lung or kidney cancer and no masses at other locations. Nevertheless a much larger study is required for definitive conclusions on a survival rate. We believe that a mini-invasive procedure such as laparoscopy may allow us to replace a rational surgical approach with a more certain pathologic diagnosis.

Adenoma↗
PubMed2001

Centrally mediated effects of bromocriptine on cardiac sympathovagal balance.

Bromocriptine, a dopamine agonist, is known to lower cardiovascular mortality in L-dopa-treated patients with Parkinson's disease, probably by reducing the cardiac sympathetic activity. We aimed at unmasking the central effects of bromocriptine on the heart by power spectrum analysis. Ten healthy subjects (aged 31+/-2 years) in supine and sitting positions were evaluated after the administration of bromocriptine (2.5 mg) alone and after pharmacological peripheral D(2)-like blockade by domperidone (20 mg). We calculated (autoregressive method) the following: the low-frequency (LF) component (an index of cardiac sympathetic tone), the high-frequency (HF) component (an index of cardiac vagal tone), and the LF/HF ratio (an index of cardiac sympathovagal balance). With subjects in the supine position, bromocriptine alone induced a significant increase in the LF component and the LF/HF ratio, together with a reduction in norepinephrine plasma levels and blood pressure values. These conflicting effects can be explained as the combined result of direct and indirect (reflex-mediated) actions of bromocriptine in vivo. No changes in cardiac autonomic drive were observed with subjects in the sitting position. After domperidone pretreatment, bromocriptine induced a reduction in the LF component and in the LF/HF ratio. The sitting position caused an increase in heart rate and in the LF/HF ratio. We demonstrated both peripheral and central effects of bromocriptine. In particular, pretreatment with a peripheral antagonist (domperidone) allowed us to unmask the central effect of bromocriptine on cardiac sympathetic drive.

Adult↗
PubMed2001

Variable expression of the transcription factors cAMP response element-binding protein and inducible cAMP early repressor in the normal adrenal cortex and in adrenocortical adenomas and carcinomas.

The molecular mechanisms leading to adrenocortical tumorigenesis have been only partially elucidated so far. Because the pituitary hormone ACTH, via activation of the cAMP pathway, regulates both cell proliferation/differentiation and steroid synthesis in the adrenal cortex, in this study we focused on the cAMP-dependent transcription factors cAMP responsive element modulator (CREM) and cAMP responsive element binding protein (CREB). We studied CREM and CREB expression by RT-PCR in human normal adrenal cortex (n = 3), adrenocortical adenomas (n = 8), and carcinomas (n = 8). We found transcripts corresponding to the isoforms alpha, beta, gamma, and tau2 of the CREM gene in all of the normal adrenal tissues, in the adenomas, and in seven of eight carcinomas. On the other hand, mRNA for the inducible cAMP early repressor isoforms, which derive from an internal promoter of CREM gene, was detected in the normal adrenal and in seven of eight adenomas, but in only three of eight carcinomas. Similarly, CREB transcripts were readily detectable in all normal adrenals and adenomas, whereas they were not found in four of eight adrenal carcinomas. To further characterize the carcinomas, telomerase activity and the expression of the ACTH receptor gene were determined. Telomerase activity in the carcinomas resulted in levels significantly higher than in the adenomas, whereas the levels of ACTH receptor mRNA were lower in the carcinomas. No correlation was found in the carcinomas between the levels of the ACTH receptor transcript and the loss of expression of CREB/inducible cAMP early repressor, suggesting that this alteration is not secondary to an upstream disregulation at the receptor level. In conclusion, our results suggest that an alteration in cAMP signaling may be associated with malignancies of the adrenal cortex.

Adenoma↗
PubMed2001

Guidelines for diagnosis and therapy of MEN type 1 and type 2.

This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

Humans↗
PubMed2001

Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes.

This study examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and of phenylethanolamine N-methyltransferase (PNMT), the enzyme that converts norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma catecholamines and metanephrines, and tumor cell neurochemistry and expression of TH and PNMT were examined in 19 MEN 2 patients and 30 VHL patients with adrenal pheochromocytomas. MEN 2 patients were more symptomatic and had a higher incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of metanephrines, but paradoxically lower total plasma concentrations of catecholamines, than VHL patients. MEN 2 patients all had elevated plasma concentrations of the epinephrine metabolite, metanephrine, whereas VHL patients showed specific increases in the norepinephrine metabolite, normetanephrine. The above differences in clinical presentation were largely explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT in pheochromocytomas from VHL than from MEN 2 patients. Thus, mutation-dependent differences in the expression of genes controlling catecholamine synthesis represent molecular mechanisms linking the underlying mutation to differences in clinical presentation of pheochromocytoma in patients with MEN 2 and the VHL syndrome.

Adolescent↗
PubMed2001

Cushing's syndrome due to intermittent ectopic ACTH production showing a temporary remission during a pulmonary infection.

OBJECTIVES: In about 15-20% of patients with ACTH-dependent Cushing's syndrome the source of ACTH is outside the pituitary gland. Pulmonary tumours are the most frequent, yet not unique, source of ectopic ACTH. In some instances the localisation of an ACTH-secreting tumour may be problematic. Occult ectopic ACTH secretion indicates the occurrence of ACTH-dependent hypercortisolism with an unknown origin. Another peculiarity of Cushing's syndrome may reside in the episodic cortisol hypersecretion, which can determine a pattern characterised by hypercortisolism together with periods of remission (cyclic Cushing's syndrome). We describe a very challenging case of Cushing's syndrome due to ectopic ACTH hypersecretion, showing virtually all of the most unusual features of the disease. DESIGN: A 55-year-old woman affected by Cushing's syndrome, presenting with biochemical features of ectopic ACTH secretion, has been followed for 7 years. METHODS: Thorough basal and dynamic hormonal assessment through the past 7 years is reported. In addition, the results of extensive imaging studies are presented. RESULTS: The source of ACTH secretion has not been identified so far, and hypercortisolism has been controlled by octreotide treatment. In addition, the patient showed a cyclic pattern of hypercortisolism with a long-term remission period. A unique feature of this case is represented by the fact that we observed a temporary, yet dramatic, short-lasting remission of ACTH and cortisol hypersecretion during a pulmonary infection, which occurred while the patient was hospitalised for a periodic hormonal assessment. CONCLUSIONS: This case well represents the wide spectrum of clinical variability of Cushing's syndrome. Most interestingly, to our knowledge, this is the first report of a case of Cushing's syndrome showing a remission during an acute infection.

Adrenocorticotropic Hormone↗
PubMed2000

Relative expression of the RET9 and RET51 isoforms in human pheochromocytomas.

Activating mutations of the RET oncogene cause the inheritance of multiple endocrine neoplasia type 2 (MEN2). The RET pre-mRNA is spliced into several transcripts coding for multiple isoforms, including Ret9 and Ret51. When harboring activating mutations in the cytoplasmic region, the Ret51 protein displays a higher in vitro transforming efficiency as compared to the corresponding Ret9 isoform. We investigated whether a more transforming isoform was preferentially expressed in MEN2 tumors as compared to normal tissues or sporadic pheochromocytomas. By quantitative RNases protection assays, we measured the absolute abundance of the 3' splice variants in pheochromocytomas and in normal tissues. The proportion of RET51 transcripts was highly dispersed between tumors and normal tissues. In familial tumors the proportion of RET51 transcripts was significantly larger (48.1%) than in sporadic tumors (36.75%). This result suggests that the preferential expression of the Ret51 protein isoform, even though moderate, is a growth advantage for MEN2 tumors.

Adrenal Gland Neoplasms↗
PubMed2000

Telomerase activity is significantly enhanced in malignant adrenocortical tumors in comparison to benign adrenocortical adenomas.

Telomerase is an enzyme that causes short repeated sequence addition to the ends of chromosomes, thereby preventing their shortening during cell division and counteracting cell senescence. Telomerase activity is generally absent in adult differentiated cells, whereas it has been demonstrated in tumor cells, suggesting that its presence might be considered an index of malignancy. To evaluate whether telomerase might be considered a good predictive index of malignancy in adrenocortical tumors, we measured telomerase activity in 11 adrenal adenomas and 7 carcinomas obtained at surgery, using an original quantitative method. Telomerase activity was significantly higher (P<0.001) in carcinomas than in adenomas (median, 15.2 ng DNA/microg protein; range, 9.0-27.6 vs. 2.0; range, 0-8.3), and no overlap was observed between the 2 groups. In carcinomas, telomerase activity was significantly correlated with tumor diameter (r = 0.939; P<0.0001), whereas in adenomas it was not. The results of this study suggest that quantitative telomerase measurement may represent a useful tool to differentiate malignant from benign adrenocortical tumors.

Adenoma↗
PubMed1999

In vivo evidence that endogenous dopamine modulates sympathetic activity in man.

Dopamine receptors type 2 (D2)-like receptor blockers cause an increase in the norepinephrine response to intense physical exercise. However, during intense physical exercise, D2-like antagonists also cause an increase in the epinephrine response, which itself might cause an increase in plasma norepinephrine through the activation of beta2 presynaptic receptors. Therefore, we evaluated the effect of domperidone, a D2-like antagonist, on the norepinephrine response to physical exercise in 6 Addison patients (3 were adrenalectomized and 3 had adrenal tuberculosis). In these patients, the norepinephrine increase observed during exercise was significantly higher after the administration of domperidone than a placebo (F=4,328; P<0.001). Because peripheral plasma norepinephrine does not reflect the sympathetic tone to the heart accurately, we evaluated the effect of domperidone administration (20 mg orally) on the sympathovagal balance, which was measured by the ratio between the high- and low-frequency components of heart rate variability, in 9 normal volunteers in the supine and sitting positions. When compared with placebo, domperidone caused a significant increase in the low/high frequency ratio (P<0.05) in the sitting position without modifying basal and stimulated norepinephrine plasma levels or blood pressure. These data support a role for endogenous dopamine in modulating norepinephrine release by human sympathetic nerves in vivo.

Adrenal Gland Diseases↗
PubMed1999

Pheochromocytoma in Italy: a multicentric retrospective study.

OBJECTIVE: To conduct an epidemiological study on pheochromocytoma in Italy. METHODS: Data on 284 patients with pheochromocytoma observed between 1978 and 1997 were collected from 18 Italian centers through a questionnaire reporting epidemiological, clinical, laboratory, radiological and surgical data. RESULTS: 53.6% of the patients were females and 46.4% were males. Thirty-two tumors were discovered as incidental adrenal masses. The most frequent referred symptoms were palpitations (58.1%), headache (51.9%), sweating (48. 8%) and anxiety (35.3%). Their association was present only in 15.5% of patients. Paroxysmal symptoms were reported in 67.1% and hypertensive crises in 59.7% of patients. Normal blood pressure (systolic and diastolic) was present both in the supine and upright positions in 21.1% of patients. Among laboratory assays, urinary vanylmandelic acid (VMA) was the most widely used (58.1%) and was the least sensitive (25% of false negative results). Basal plasma catecholamines were found to be normal in 11.3% of patients but were always elevated when sampled during a hypertensive paroxysm. A clonidine suppression test was performed in 38 patients with no adverse side effects. It gave a false negative response in 2 patients. A glucagon test was performed in 21 patients. It was interrupted for acute hypertension in 52.4% of patients. Only 5/21 patients were normotensive and had normal basal plasma catecholamines. In these patients the test gave a positive response in four (80%). CT (79.6%) and I-MIBG scintigraphy (68.5%) were the most widely used methods for tumor localization. CT sensitivity was 98.9% for intra-adrenal and 90.9% for extra-adrenal tumors. MIBG sensitivity was 88.5%. In the 263 patients who underwent surgery, the tumor was intra-adrenal in 89.4%, extra-adrenal in 8.5%, intra- and extra-adrenal in 2.1%, and bilateral in 11.0% of patients. Malignancy was reported in 9.9% of cases. Surgery caused remission of hypertension in 59.3%, improvement in 26.8%, and no changes in 13. 9% of patients. In the last group the interval between initial symptoms and diagnosis was significantly longer. CONCLUSIONS: The present study confirms that the clinical presentation of pheochromocytoma is variable and aspecific. Normotension is often present and often the tumor is discovered incidentally. An indication for the routine use of screening methods more sensitive than urinary VMA is strongly suggested. The clonidine test was found to be safe and should be preferred to the glucagon test which has to be restricted to very selected patients. CT and MIBG scintigraphy are almost always successful in localizing the tumor. Reversal of hypertension by surgery seems to depend on an early diagnosis.

Adolescent↗
PubMed1999

Angiotensin II stimulates the synthesis and secretion of vascular permeability factor/vascular endothelial growth factor in human mesangial cells.

The aim of the present study was to evaluate the role of angiotensin II (AngII) in regulating both the gene expression and secretion of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in human mesangial cells (HMC) in culture. Densitometric analysis of Northern blot experiments demonstrated that AngII increases VPF/VEGF mRNA in a dose-dependent manner. The levels of VPF/VEGF mRNA in HMC exposed for 3 h to 10 nM, 100 nM, and 1 microM AngII were, respectively, 1.5-, 2.3-, and 1.6-fold higher than control cells (P < 0.05, P < 0.0001, and P < 0.05, respectively). This effect was blocked by the pretreatment with losartan (1 microM) (P < 0.005), a selective antagonist of the AngII AT1 receptor. Reverse transcription-PCR performed in HMC using oligonucleotide primers specific for all VPF/VEGF mRNA splicing variants detected three bands corresponding to VEGF 189, 165, and 121. Exposure of the cells to 100 nM AngII resulted in an increase of all the mRNA transcripts. Furthermore, in situ hybridization experiments showed that the levels of hybridization signals for VPF/VEGF mRNA resulted consistently higher in HMC exposed for 3 h to AngII (100 nM) than in control cells. The effects of AngII on the secretion of VPF/VEGF peptide in the culture medium of HMC were assessed using an enzyme-linked immunosorbent assay method. When different concentrations of AngII were tested in 3-h stimulation periods, the percentage of increase in the levels of released VPF/VEGF was significantly higher than control cells for AngII concentrations of 100 nM (62 +/- 11% mean +/- SD, P < 0.0001) and 1 microM (17.3 +/- 10.9%, P < 0.01). The pretreatment of HMC with losartan (1 microM) prevented the increase of VPF/VEGF secretion induced by AngII (100 nM) (AngII 54.7 +/- 3.9 pg/microg DNA versus AngII + losartan 37.8 +/- 3.6 pg/microg DNA, mean +/- SD, P < 0.005). VPF/VEGF protein was time dependently released in the culture medium under basal, steady-state conditions. Compared with control cells, AngII (100 nM) caused a significant increase in the levels of released VPF/VEGF after 3 and 6 h (control 33.8 +/- 1.7 pg/microg DNA at 3 h, 42.1 +/- 1.1 at 6 h, and 117.7 +/- 10 at 24 h; AngII 54.7 +/- 3.9 at 3 h, P < 0.0001, 61.6 +/- 8.7 at 6 h, P < 0.05, and 144.7 +/- 22.7 at 24 h, NS; mean +/- SD). According to the results obtained from enzyme-linked immunosorbent assay experiments, Western blot analysis showed that the intensity of the 19-kD band corresponding to VPF/VEGF was 1.5-fold higher in AngII (100 nM)-treated HMC than in control cells. Similarly, immunocytochemistry on HMC demonstrated an increase in intracellular VPF/VEGF immunostaining in response to AngII treatment (100 nM) compared with control cells. This study demonstrated that in HMC, AngII augmented the levels of VPF/VEGF gene expression and stimulated the synthesis and secretion of its peptide by activating AT1 receptors. Through these mechanisms, AngII may affect the functions of endothelial cells during the development of renal diseases involving the glomerulus.

Angiotensin II↗
PubMed1998

Effects of clonidine on power spectral analysis of heart rate variability in mild essential hypertension.

Patients with essential hypertension often show alterations of the autonomic nervous system. We evaluated the sympathetic and parasympathetic drive to the heart in 12 mildly hypertensive patients and 9 healthy subjects by power spectral analysis of heart rate variability. All subjects underwent measurements of RR interval, low (LF) and high frequency (HF) components of heart rate variability, LF/HF ratio and blood pressure in the resting and sitting positions, both before and after oral clonidine (300 microg), a central sympatholytic agent. In the supine position before clonidine, hypertensive patients had higher blood pressure and lower HF values than healthy subjects. Clonidine induced increases in RR interval and HF in both groups, while LF and LF/HF ratio decreased in healthy subjects, but not in hypertensive patients. On assuming the sitting position, both groups showed reductions in RR and HF and increments in LF and LF/HF. In healthy subjects, the response to the postural challenge was unaffected by clonidine. In contrast, hypertensive patients showed no changes in LF and LF/HF ratio, and a significantly lower decrease in HF. These differences were probably due to the existence of two subsets of patients, one exhibiting similar responses to clonidine as healthy subjects, and the other showing no appreciable response to the drug. These results suggest that hypertensive patients have an altered sympatho-vagal balance to the heart, which can be unmasked by clonidine. This phenomenon should be taken into account to achieve a better control of the overall cardiovascular risk of hypertensive patients.

Administration, Oral↗
PubMed1998

Different effects of atrial and C-type natriuretic peptide on the urinary excretion of endothelin-1 in man.

1. Following the observation that brain natriuretic peptide enhances the urinary excretion rate of endothelin-1, the relationship between natriuretic peptides and urinary endothelin-1 was further investigated. Six healthy volunteers received, on three different occasions, increasing doses of atrial or C-type natriuretic peptide (0, 2 and 4 pmol.min-1.kg-1 for 1 h each), or placebo.2. Atrial natriuretic peptide caused significant increases in the urinary excretion of cGMP, sodium and endothelin-1, without affecting plasma endothelin-1, renal plasma flow, glomerular filtration rate and urine flow rate. C-type natriuretic peptide did not modify any of these parameters. During atrial natriuretic peptide infusion, urinary endothelin-1 directly correlated with plasma atrial natriuretic peptide, urinary cGMP and sodium excretion.3. These results indicate that enhancement of the urinary excretion of endothelin-1 by natriuretic peptides is dose-dependent and somewhat related to their ability to bind to natriuretic peptide receptors A, activate guanylate cyclase and induce a natriuretic response.

Adult↗
PubMed1998

Effects of acute clonidine administration on power spectral analysis of heart rate variability in healthy humans.

1. To investigate the relationship between the autonomic drive to the heart and heart rate variability, as evaluated by power spectral analysis, we studied the effect of clonidine (300 microg), a central sympatholytic agent, on heart rate variability. 2. Six healthy subjects (mean age 31 +/- 3 years) were studied in the supine and the sitting position (15 min each) on two different occasions, respectively, before and after clonidine administration. Using an autoregressive approach, the low frequency (LF) and the high frequency (HF) components of power spectral analysis were measured, and their ratio was calculated. Blood pressure was monitored throughout the study and plasma catecholamines were measured at the end of each period. 3. Before clonidine, assumption of the sitting position induced increases in LF, LF/HF ratio, blood pressure and plasma noradrenaline. Clonidine induced remarkable reductions in the normalized values of the LF component and the LF/HF ratio in both the resting and the sitting position (supine: LF = -68%, LF/HF ratio = -80%; sitting: LF = -23%, LF/HF ratio = -55%) without affecting the central frequencies of LF and HF components. Blood pressure and plasma catecholamines also significantly decreased after clonidine. 4. These results support the hypothesis that the LF component of HRV, expressed in normalized units, is an indicator of the sympathetic control of the heart. In addition, this component seems to be largely of central origin, because it is markedly reduced by the central sympatholytic action of clonidine.

Adult↗
PubMed1998

Low-dose C-type natriuretic peptide does not affect cardiac and renal function in humans.

In experimental animals, C-type natriuretic peptide (CNP) has vasodilating, hypotensive, and natriuretic activities. The role of circulating CNP in the overall regulation of cardiac and renal function in humans is less defined, in both health and disease. We measured cardiac volumes, diastolic and systolic functions, systemic (Doppler echocardiography) and renal hemodynamics, intrarenal sodium handling (lithium clearance method), plasma and urinary cGMP, plasma renin concentration, and plasma aldosterone level in six healthy volunteers (mean age, 33+/-3 years) receiving CNP (2 and 4 pmol/kg per minute for 1 hour each) in a single-blind, placebo-controlled, random-order, crossover study. During CNP infusion, plasma CNP increased from 1.17+/-0.23 to 41.52+/-4.61 pmol/L (ie, 4- to 10-fold higher levels than those observed in disease states) without affecting plasma and urinary cGMP, cardiac volumes, dynamics of left and right heart filling, cardiac output, arterial pressure, renal hemodynamics, intrarenal sodium handling, sodium excretion, or plasma levels of renin and aldosterone. The finding that increments in plasma CNP within the pathophysiological range have no effects on systemic hemodynamics, renal function, or the renin-angiotensin system do not support the hypothesis that CNP may act as a circulating hormone in humans.

Adult↗