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Biomedical subjects

B E Fernández

Publications and source records attributed to B E Fernández.

At least 19 recordsLinked to original sources
PubMed2006

Acute sodium overload produces renal tubulointerstitial inflammation in normal rats.

The aim of the present study was to determine whether acute sodium overload could trigger an inflammatory reaction in the tubulointerstitial (TI) compartment in normal rats. Four groups of Sprague-Dawley rats received increasing NaCl concentrations by intravenous infusion. Control (C): Na+ 0.15 M; G1: Na+ 0.5 M; G2: Na+ 1.0 M; and G3: Na+ 1.5 M. Creatinine clearance, mean arterial pressure (MAP), renal blood flow (RBF), and sodium fractional excretion were determined. Transforming growth factor beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), RANTES, transcription factor nuclear factor-kappa B (NF-kappaB), and angiotensin II (ANG II) were evaluated in kidneys by immunohistochemistry. Animals with NaCl overload showed normal glomerular function without MAP and RBF modifications and exhibited a concentration-dependent natriuretic response. Plasmatic sodium increased in G2 (P < 0.01) and G3 (P < 0.001). Light microscopy did not show renal morphological damage. Immunohistochemistry revealed an increased number of ANG II-positive tubular cells in G2 and G3, and positive immunostaining for NF-kappaB only in G3 (P < 0.01). Increased staining of alpha-SMA in the interstitium (P < 0.01), TGF-beta1 in tubular cells (P < 0.01), and a significant percentage (P < 0.01) of positive immunostaining for RANTES in tubular epithelium and in glomerular and peritubular endothelium were detected in G3 > G2 > C group. These results suggest that an acute sodium overload is able 'per se' to initiate TI endothelial inflammatory reaction (glomerular and peritubular) and incipient fibrosis in normal rats, independently of hemodynamic modifications. Furthermore, these findings are consistent with the possibility that activation of NF-kappaB and local ANG II may be involved in the pathway of this inflammatory process.

Actins↗
PubMed2001

Behavior of atrial natriuretic factor in an experimental model of Trypanosoma cruzi infection in rats.

Enhanced atrial natriuretic factor (ANF) production by the heart is related to hemodynamic overload, cardiac growth, and hypertrophy. The heart is one of the most affected organs during Trypanosoma cruzi infection. We tested the hypothesis that myocarditis produced by parasite infection alters the natriuretic peptide system by investigating the behavior of plasma ANF during the acute and chronic stages of T. cruzi infection in rats. Sprague-Dawley rats were infected with T. cruzi clone Sylvio-X10/7. Cardiac morphology showed damage to myocardial cells and lymphocyte infiltration in the acute phase; and fibrosis and cell atrophy in the chronic period. Plasma ANF levels (radioimmunoassay) were significantly higher in acute (348 +/- 40 vs. 195 +/- 36 pg/ml, P < 0.05, n = 17) and chronic T. cruzi myocarditis (545 +/- 81 vs. 229 +/- 38 pg/ml, P < 0.001, n = 11) than in their respective controls (n = 10 and 14). Rats in the chronic phase also showed higher levels than rats in the acute phase (P < 0.01). The damage of myocardial cells produced by the parasite and the subsequent inflammatory response could be responsible for the elevation of plasma ANF during the acute period of T. cruzi infection. The highest plasma ANF levels found in chronically infected rats could be derived from the progressive failure of cardiac function.

Acute Disease↗
PubMed2000

Central natriuretic peptides regulation of peripheral atrial natriuretic factor release.

Atrial natriuretic factor (ANF) and C-type natriuretic peptide (CNP) receptors have been described in encephalic areas and nuclei related to the regulation of cardiovascular as well as sodium and water homeostasis. Stimulation of the anterior ventral third ventricular region of the brain modifies plasma ANF concentration, suggesting the participation of the central nervous system in the regulation of circulating ANF. The aim of this work was to study the effect of centrally applied ANF or CNP on plasma ANF. Normal and blood volume expanded rats (0.8 ml isotonic saline/100 g body weight) were intra cerebralventricularly injected with 1, 10 or 100 ng/microl/min ANF. Blood volume expanded animals were also centrally injected with the same doses of CNP. Blood samples were collected at 5 and 15 min. after intracerebralventricular administration of either ANF or CNP. Centrally applied ANF did not affect circulating ANF in normal blood volume rats. In blood volume expanded animals both ANF (1, 10 or 100 ng/microl/min) and CNP (1 ng/microl/min) decreased plasma ANF concentration after 15 min. Moreover, CNP (10 and 100 ng/microl/min) lowered circulating ANF levels not only at 15 min but also at 5 min. Neither ANF nor CNP elicited any change in mean arterial pressure and heart rate in normal and blood volume expanded rats. These results suggest the existence of a central regulation exerted by natriuretic peptides on circulating ANF levels. Furthermore, this is the first study reporting an effect on plasma ANF induced by centrally applied CNP.

Animals↗
PubMed2000

B-Type and C-type natriuretic peptides modify norepinephrine uptake in discrete encephalic nuclei of the rat.

1. We previously demonstrated that atrial natriuretic factor and B- and C-type natriuretic peptides (ANF, BNP, and CNP, respectively) modified catecholamine metabolism by increasing the neuronal uptake and decreasing the neuronal release of norepinephrine in the rat hypothalamus. The aim of the present work was to study the effects of natriuretic peptides BNP and CNP on norepinephrine uptake as an index of the amine metabolism in discrete areas and nuclei of the central nervous system (CNS) of the rat. 2. Experiments were carried out in vitro using the punchout technique in diverse areas and nuclei of rat CNS. Results showed that 100 nM BNP and 1 nM CNP increased norepinephrine (NE) uptake in all brain areas and nuclei studied. 3. Present results permit us to conclude that BNP and CNP regulate NE metabolism independently of the encephalic area or nucleus involved. In fact, NE uptake increased in nuclei related to the regulation of cardiovascular activity as well as nuclei associated with endocrine metabolism and hydrosaline homeostasis. These observations suggest that BNP and CNP may be involved in the regulation of these physiological processes in an indirect manner through modifications of noradrenergic neurotransmission. Present findings provide further support to the hypothesis that CNP would be the main natriuretic peptide in brain. Furthermore, previous as well as present results support the role of the natriureic peptides as neuromodulators of noradrenergic transmission at the presynaptic level.

Animals↗
PubMed2000

Angiotensin-(1-7) reduces norepinephrine release through a nitric oxide mechanism in rat hypothalamus.

Angiotensin (Ang)-(1-7) elicits a facilitatory presynaptic effect on peripheral noradrenergic neurotransmission, and because biological responses to the heptapeptide on occasion are tissue specific, the present investigation was undertaken to study its action on noradrenergic neurotransmission at the central level. In rat hypothalamus labeled with [(3)H]-norepinephrine, 100 to 600 nmol/L Ang-(1-7) diminished norepinephrine released by 25 mmol/L KCl. This effect was blocked by the selective angiotensin type 2 receptor antagonist PD 123319 (1 micromol/L) and by the specific Ang-(1-7) receptor antagonist ([D-Ala(7)]Ang-(1-7) (1 micromol/L) but not by losartan (10 nmol/L to 1 micromol/L), a selective angiotensin type 1 receptor antagonist. The inhibitory effect on noradrenergic neurotransmission caused by Ang-(1-7) was prevented by 10 micromol/L N(omega)-nitro-L-arginine methylester, an inhibitor of nitric oxide synthase activity, and was restored by 100 micromol/L L-arginine, precursor of nitric oxide synthesis. Methylene blue (10 micromol/L), an inhibitor of guanylate cyclase considered as the target of nitric oxide action, as well as Hoe 140 (10 micromol/L), a bradykinin B(2)-receptor antagonist, prevented the inhibitory effect of the heptapeptide on neuronal norepinephrine release, whereas no modification was observed in the presence of 0.1 to 10 micromol/L indomethacin, a cyclooxygenase inhibitor. Our results indicate that Ang-(1-7) has a tissue-specific neuromodulatory effect on noradrenergic neurotransmission, being inhibitory at the central nervous system by a nitric oxide-dependent mechanism that involves angiotensin type 2 receptors and local bradykinin production.

Angiotensin I↗
PubMed1999

Atrial natriuretic factor inhibits norepinephrine biosynthesis and turnover in the rat hypothalamus.

We have previously reported that atrial natriuretic factor (ANF) increased neuronal norepinephrine (NE) uptake and reduced basal and evoked neuronal NE release. Changes in NE uptake and release are generally associated to modifications in the synthesis and/or turnover of the amine. On this basis, the aim of the present work was to study ANF effects in the rat hypothalamus on the following processes: endogenous content, utilization and turn-over of NE; tyrosine hydroxylase (TH) activity; cAMP and cGMP accumulation and phosphatidylinositol hydrolysis. Results showed that centrally applied ANF (100 ng/microl/min) increased the endogenous content of NE (45%) and diminished NE utilization. Ten nM ANF reduced the turnover of NE (53%). In addition, ANF (10 nM) inhibited basal and evoked (with 25 mM KCl) TH activity (30 and 64%, respectively). Cyclic GMP levels were increased by 10 nM ANF (100%). However, neither cAMP accumulation nor phosphatidylinositol breakdown were affected in the presence of 10 nM ANF. The results further support the role of ANF in the regulation of NE metabolism in the rat hypothalamus. ANF is likely to act as a negative putative neuromodulator inhibiting noradrenergic neurotransmission by signaling through the activation of guanylate cyclase. Thus, ANF may be involved in the regulation of several central as well as peripheral physiological processes such as cardiovascular function, electrolyte and fluid homeostasis, endocrine and neuroendocrine synthesis and secretion, behavior, thirst, appetite and anxiety that are mediated by central noradrenergic activity.

Animals↗
PubMed1999

Increased plasma atrial natriuretic factor in catecholamine-producing tumor patients.

The aim of this study was to evaluate plasma levels of ANF in patients with catecholamine-secreting tumors with and without hypertension and to relate ANF secretion to levels of plasma and urinary catecholamines and blood pressure. Twenty-one pheochromocytoma (15 with sustained, 6 with paroxysmal hypertension), 6 neuroblastoma (1 hypertensive) patients and 28 aged-matched controls were studied in basal conditions. Plasma and urinary norepinephrine (NE),epinephrine (E), dopamine (DA) and DOPA were determined by HPLC-ED and plasma ANF by RIA. Both neuroblastoma and pheochromocytoma patients had significantly higher plasma ANF levels than controls. Neuroblastomas showed higher ANF concentration than pheochromocytomas. No differences were found in plasma ANF between hypertensive and normotensive patients. Pheochromocytomas with ANF levels within the normal range had plasma and urinary NE and urinary DA and DOPA levels significantly higher than patients with high ANF. Plasma ANF levels were unrelated to systolic or diastolic blood pressure or heart rate. A negative correlation between plasma ANF and urinary DA was found only in the patients groups. In conclusion, plasma ANF was increased in pheochromocytoma and neuroblastoma patients. Our data suggest that the excessive catecholamine secretion is not responsible for the increased ANF secretion in these patients. The significance of the relationships among plasma ANF and urinary and plasma catecholamines requires further investigation.

Abdominal Neoplasms↗
PubMed1998

Atrial natriuretic factor in two kidney--two clip renovascular hypertension in the rat.

Hig levels of circulating atrial natriuretic factor (ANF) have been reported in several physiopathologic conditions like hypertension, heart and renal failure, pregnancy and high sodium intake. Nevertheless, neither relationships with water-sodium space regulation nor the role of an ANF vascular relaxant effect have been yet defined. The aim of present experiments was to characterize the contribution of circulating ANF and its vascular relaxing effects in the two kidney-two clip (2K2C) experimental model of renovascular hypertension. Complementary, plasma metabolites nitrite/nitrate of nitric oxide (NO) was examined because of mediation for both (NO an ANF) through cGMP. Three results showed (two-four weeks after surgery): indirect systolic blood pressure (mmHg), 186 +/- 4 in HT and 122 +/- 1 in SH (p < 0.001); a significant increase of plasma ANF (fmol/ml) in HT (n = 7, 1221 +/- 253) vs. SH (n = 9, 476 +/- 82; p < 0.02). Nitrate/nitrite plasma concentrations (mumol/l) were mpt different between SH and. The relaxant effect of ANF (10(-9), 10(-8) and 10(-7) M) on phenylephrine (3,5 x 10(-6) M) contracted rings from HT rats was smaller than SH rats (10(-8) M, p < 0.05). Contractions to phorbol 12, 13-dibutyrate (seven weeks after surgery) were significantly higher in rings from HT rats (p < 0.001). We conclude: 1) in addition to decreased granularity in atrial myocardiocytes, high circulating values of ANF here described suggest an increased turnover of the peptide in 2K2C hypertensive rats; 2) lower significant vascular relaxant effects in HT rats would indicate down regulation of ANF receptors in this model; the latter would derive from high plasma ANF concentration and, tentatively, because of greater activity of protein kinase C in the vascular wall; 39 similar values of plasma nitrite/nitrate in SH and HT rats would indicate a comparable NO circulating availability in both groups.

Animals↗
PubMed1997

Atrial natriuretic factor modifies the biosynthesis and turnover of norepinephrine in the rat adrenal medulla.

In the present work we investigate atrial natriuretic factor (ANF) effects on the endogenous content, utilization and turn over of norepinephrine (NE), on tyrosine hydroxilase (TH) activity, on cAMP and cGMP levels, and on phosphatidylinositol hydrolysis in rat adrenal medulla in order to assess the possible mechanisms underlying ANF effects on NE metabolism. Results showed that ANF (5 microg/kg) increased NE endogenous content (44%) and diminished the amine utilization. On the other hand, the atrial factor (10 nM) inhibited both spontaneous and evoked, by 100 mM KCl TH, activity (48% and 59%, respectively). When second messenger systems were studied results showed that 10 nM ANF increased cGMP levels in adrenal medulla (51%), while it modified neither cAMP levels nor phosphatidylinositol hydrolysis. These results suggest that ANF may play an important role in the modulation of the sympathoadrenergic system function, behaving as a putative neuromodulator.

Adrenal Medulla↗
PubMed1996

B and C types natriuretic peptides modulate norepinephrine uptake and release in the rat hypothalamus.

We previously reported that atrial natriuretic factor (ANF) regulates catecholamine metabolism in the central nervous system. ANF, B and C types natriuretic peptides (BNP and CNP) also play a regulatory role in body fluid homeostasis, cardiovascular activity and hormonal and neuro-hormonal secretions. The aim of the present work was to investigate BNP and CNP effects on the uptake and release of norepinephrine (NE) in rat hypothalamic slices incubated in vitro. Results showed that BNP (100 nM) and CNP (1, 10 and 100 nM) enhanced total and neuronal [3H]NE uptake but did not modify non-neuronal uptake. BNP (100 nM) and CNP (1 nM) caused a rapid increase in NE uptake (1 min), which was sustained for 60 min. BNP (100 nM) did not modify the intracellular distribution of NE; however, 1 nM CNP increased the granular store and decreased the cytosolic pool of NE. BNP (100 nM) and CNP (1, 10 and 100 nM), diminished spontaneous NE release. In addition, BNP (1, 10, 100 nM) and CNP (1, 10 and 100 pM, as well as 1, 10 and 100 nM) reduced NE output induced by 25 mM KCl. These results suggest that BNP and CNP may be involved in the regulation of several central as well as peripheral physiological functions through the modulation of noradrenergic neurotransmission at the presynaptic neuronal level. Present results provide evidence to consider CNP as the brain natriuretic peptide since physiological concentrations of this peptide (pM) diminished NE evoked release.

Animals↗
PubMed1996

Atrial natriuretic factor modifies the composition of induced-salivary secretion in the rat.

We have previously reported that although the atrial natriuretic factor (ANF) was not a sialogogic agonist, it enhanced cholinergic, alpha-adrenergic and peptidergic (substance P) stimulated salivation in the submaxillary and parotid gland of the rat. The purpose of the present work was to study whether ANF modified the composition of agonist-induced saliva in the rat. Results showed that in the submaxillary gland, ANF increased sodium and decreased potassium excretion when salivation was stimulated by methacholine (MC) or substance P (SP). However, when salivation was induced by methoxamine (MX), ANF only increased sodium excretion. On the other hand, in the parotid gland, ANF increased both sodium and potassium excretion when salivation was induced either by MC or SP but did not modify electrolyte output in MX induced salivary secretion. Protein output and amylase activity were not modified by the presence of ANF when the aforementioned sialogogic agonists were used to elicit salivation in either gland. Although ANF did not modify the volume of isoproterenol (IP) induced saliva, it increased protein output in both glands and it increased amylase activity in the parotid gland. The present results suggest that ANF may play a role in the modulation of salivary secretion in the parotid and submaxillary glands of the rat. ANF effect is likely to be mediated by modifications in the calcium level linked to phosphoinositide metabolism within the acinar and/or the ductal cells of the salivary glands.

Animals↗
PubMed1995

Angiotensin III modulates noradrenaline uptake and release in the rat hypothalamus.

1. Effects of angiotensin III (A III) on 3H-noradrenaline (3H-NA) total, neuronal and non-neuronal uptake, 3H intracellular distribution and release were studied in vitro in the rat hypothalamus. 2. A III (1 microM) decreased total, neuronal and non-neuronal 3H-NA uptake when hypothalamic slices were incubated with 3H-NA for 30 min. A III effects on neuronal and non-neuronal 3H-NA uptake were determined in the presence of 100 microM hydrocortisone or 10 microM cocaine hydrochloride, respectively. The effect of A III on total 3H-NA uptake was blocked by 10 microM Ile7 angiotensin III (Ile7 A III), an antagonist at A III receptors. In contrast, 100 nM A III had no effect on 3H-NA uptake. 3. The study of the 3H-NA uptake time course showed that 1 microM AIII decreased NA uptake at 1, 3, 7, 15 and 30 min incubation. 4. In hypothalamic slices preloaded with 3H-NA for 30 min, 1 microM AIII increased the 3H content in the granular pool and decreased it in the cytosolic pool. 5. Spontaneous 3H release was also modified by 1 microM A III when hypothalami were preloaded with 3H-NA for 30 min. A III increased the spontaneous output of 3H. This effect was receptor-mediated since the effect of A III on 3H release was antagonized by Ile7 A III. 6. The present results suggest that the effects of A III on NA neurotransmission, may be involved in the regulation of central angiotensin effects such as blood pressure control, hydrosaline balance and dipsogenesis, through modulation of central sympathetic activity.

Angiotensin III↗
PubMed1995

Effects of atrial natriuretic factor on norepinephrine release evoked by angiotensins II and III in the rat adrenal medulla.

Atrial natriuretic factor (ANF) effects on neuronal norepinephrine (NE) release evoked by angiotensin II (ANG II) or angiotensin III (ANG III) were studied in the rat adrenal medulla. ANF 10 nM diminished the increase of NE release induced by ANG II (1 microM), ANG III (1 microM) or 100 mM KCl. When 10 nM ANF was added to the medium containing KCl plus ANG II or KCl plus ANG III, the reduction of 3H-NE output by ANF was greater than when the atrial factor was added to the medium containing only ANG II or ANG III. Since both ANG II and ANG III have a physiological role on catecholamine metabolism, these peptides could modulate the adrenal medulla functions. ANG II and ANG III enhance NE release and decrease NE uptake in the rat adrenal medulla. Present results show that ANF is a physiological antagonist of both ANG II and ANG III, in the process of NE secretion. The interaction between ANF and the renin-angiotensin system could contribute to the regulation of the adrenal medulla catecholamines pathway and sympathetic activity.

Adrenal Medulla↗
PubMed1994

Atrial natriuretic factor enhances induced salivary secretion in the rat.

As atrial natriuretic factor (ANF) is intimately involved in water and electrolyte homeostasis, dose-response studies were performed in the parotid as well as submaxillary glands of the rat with increasing doses of the atrial peptide to investigate its possible role as a sialogogic agent. Dose-response studies were also performed in both salivary glands with different pharmacological agonists known to cause salivation in the rat (methacholine, noradrenaline, isoproterenol, methoxamine and substance P) in the absence and in the presence of ANF. The atrial factor did not induce salivation 'per se' at least in the investigated doses. However, it enhanced the salivary response to methacholine, methoxamine and substance P but it did not modify the salivation induced either by noradrenaline or isoproterenol. The present results showed that ANF enhanced the salivation induced by pharmacological agents which stimulate phosphatidylinositol hydrolysis. These effects of ANF may be probably related to the activation of the non-guanylate cyclase coupled receptor which has been associated with phosphatidylinositol turnover. Nevertheless, although the atrial factor induces vasorelaxation, its enhancement of blood flow may not be the major event underlying the present results. The present work suggests a potential physiological role of ANF on the modulation of salivary secretion and provides further evidence on the rol of ANF in the regulation of body fluid homeostasis.

Animals↗
PubMed1992

Effects of atrial natriuretic factor on norepinephrine release in the rat hypothalamus.

The effects of atrial natriuretic factor on the mechanisms involved in norepinephrine release were studied 'in vitro' in slices of Wistar rat hypothalamus. Atrial natriuretic factor (10, 50 and 100 nM) decreased spontaneous [3H]norepinephrine secretion in a concentration dependent way. In addition, the peptide (10 nM) also reduced acetylcholine induced output of norepinephrine. The atrial factor (10 nM) was unable to alter the amine secretion when the incubation medium was deprived of calcium or when a calcium channel blocker such as diltiazem (100 microM) was added. In conclusion, atrial natriuretic factor reduced both spontaneous and acetylcholine evoked [3H]norepinephrine release in the rat hypothalamus. These findings suggest that the atrial natriuretic factor may alter catecholamine secretion by modifying the calcium available for the exocytotic process of catecholamine output.

Acetylcholine↗
PubMed1992

Monophasic and biphasic effects of angiotensin II and III on norepinephrine uptake and release in rat adrenal medulla.

Angiotensin II and III have hypertensive effects. They induce vascular smooth muscle constriction, increase sodium reabsorption by renal tubules, stimulate the anteroventral third ventricle area, increase vasopressin and aldosterone secretions, and modify catecholamine metabolism. In this work, angiotensin II and III effects on norepinephrine uptake and release in rat adrenal medulla were investigated. Both angiotensins decreased total and neuronal norepinephrine uptake. Angiotensin II showed a biphasic effect only on evoked neuronal norepinephrine release (an earlier decrease followed by a later increase), while increasing the spontaneous norepinephrine release only after 12 min. On the other hand, angiotensin III showed a biphasic effect on evoked and spontaneous neuronal norepinephrine release. Both angiotensins altered norepinephrine distribution into intracellular stores, concentrating the amine into the granular pool and decreasing the cytosolic store. The results suggest a physiological biphasic effect of angiotensin II as well as angiotensin III that may be involved in the modulation of sympathetic activity in the rat adrenal medulla.

Adrenal Medulla↗
PubMed1992

Effects of atrial natriuretic peptide, angiotensin II and III on norepinephrine uptake in the rat adrenal medulla.

The effects of atrial natriuretic peptide (ANP), angiotensin II (ANG II) and angiotensin III (ANG III) on norepinephrine (NE) uptake were studied in the adrenal medulla of the rat. One microM ANG II and 10 microM ANG III decreased NE uptake while 10 nM and 100 nM ANP increased it. Subthreshold concentrations of ANP (1 nM) blunted the inhibitory effect of 1 microM ANG II but did not modify the inhibitory effect of 10 microM ANG III. The increasing effects of 100 nM ANP on NE uptake were partially reversed by subthreshold concentrations of ANG II (1 nM) and blunted by 1 nM ANG III. The interaction between ANP and the renin-angiotensin system could contribute to modulate the sympathetic function in the adrenal medulla.

Adrenal Medulla↗