Atrial natriuretic peptide reduces inflammation and enhances apoptosis in rat acute pancreatitis.

AIM: We previously reported that atrial natriuretic peptide (ANP) reduces serum amylase and intrapancreatic trypsinogen activation in the onset of acute pancreatitis whereas secretin increases them. In the present work, we sought to establish the effect of ANP and secretin on the inflammatory response and cell death in experimental acute pancreatitis. METHODS: The expression and activity of key inflammatory mediators and apoptosis were evaluated in the presence or absence of the atrial peptide, secretin or both in cerulein-induced acute pancreatitis in rats. Also, ultrastructural changes in pancreatic acinar cells were assessed by transmission electron microscopy. RESULTS: ANP significantly reduced NF-κB activation and TNF-α intrapancreatic levels. Furthermore, it decreased inducible nitric oxide synthase and cyclooxygenase 2 expression and activity while it diminished myeloperoxidase activity. ANP also stimulated apoptosis as shown by caspase-3 expression and activation as well as TUNEL assay. These findings correlated well with the ultrastructural changes observed in the exocrine pancreas. Although secretin reduced various inflammatory markers, it also diminished caspase-3 activation and the overall response was the aggravation of the disease as reflected by the ultrastructural alterations of pancreatic acinar cells. In the presence of ANP, various effects evoked by secretin were antagonized. CONCLUSION: Present findings show that ANP significantly attenuated the severity of acute pancreatitis in the rat by inducing apoptosis and reducing the inflammatory response and further suggest that ANP may have eventual therapeutic implications in the disease and/or in medical interventions at risk of its developing like endoscopic retrograde cholangiopancreatography.

Protein free diet feeding: effects on sympathetic activity and salivary evoked secretion in the submandibular gland of the rat.

Protein restriction impairs the salivary flow rate and composition in human and rats. The aim of the present work was to establish the effect of low protein (casein 5%) and protein free (casein 0%) isocaloric diets on sympathetic activity and salivary evoked secretion in the submandibular gland (SMG) of the rat. After 21 days, rats fed casein 0% presented: (a) a significant shift to the left of the dose-response curves (DRC) to the autonomic agonists-norepinephrine (NE), methoxamine, isoproterenol (ISO) and methacholine; (b) increased food consumption (p<0.001); (c) decreased body (p<0.001) and SMG (p<0.001) weights maintaining SMG/body (w/w) relation; (d) enhanced submandibular alpha1-adrenoceptor number without changes in the apparent dissociation constant (Kd); (e) increased submandibular NE content (p<0.05) and phosphoinositoside hydrolysis (p<0.001); (f) decreased submandibular tyrosine hydroxylase activity (TH) (p<0.01). Casein 5% feeding increased food consumption (p<0.01) and reduced body weight (p<0.05). This protein restriction increased metacholine-evoked salivation, but it altered neither submandibular sympathetic activity nor sympathetic-induced salivary secretion as compared to the Control group (C) fed a similar diet containing 25.5% protein. Present results suggest that in the adult rat, a protein free diet during 21 days lowers SMG sympathetic and cholinergic activity leading to supersensitivity as revealed by up-regulation of alpha1-adrenergic receptor number and increased autonomic-evoked salivation.

Salivary glands and noradrenergic transmission in diabetic rats.

1 Type 2 diabetes is associated with diverse oral pathologies in which salivary flow reduction is one of the causes of these oral abnormalities. Scarce literature exists regarding noradrenergic transmission and adrenergic-induced salivary flow in submaxillary and parotid glands of type 2 diabetic rats. 2 We studied noradrenergic transmission as well as the secretory response to alpha1- and beta-adrenoceptor stimulation in the parotid and submaxillary glands of type 2 diabetic rats. 3 Diabetic rats exhibited diminished neuronal uptake, release and endogenous content of noradrenaline (NE) in both salivary glands. Further, NE synthesis was also diminished accompanied by decreased tyrosine hydroxylase activity. Salivary flow responses to alpha1-(methoxamine) and beta-(isoprenaline) adrenoceptor stimulation were reduced in the submaxillary as well as the parotid glands of diabetic rats. 4 Our results suggest that the reduction of noradrenergic transmission in the salivary glands of type 2 diabetic rats is in part responsible for the diminished salivary flow evoked by alpha1- and beta-adrenergic stimulation. Reduced noradrenergic activity may contribute to the pathophysiology of oral abnormalities in diabetic patients.

Cyclosporin A: effects on the secretory process and noradrenergic activity in the submandibular gland of the rat.

OBJECTIVES: The aim of the present work was to study the effect of long-term cyclosporine (CSA) administration on norepinephrine (NE) metabolism and adrenergic-evoked secretion in the rat submandibular gland (SMG). METHODS: Dose-response curves to adrenergic agonists (methoxamine, isoproterenol, NE) were performed in control and CSA (10 and 30 mg/kg every 2 days for 1 month)-treated rats after SMG duct cannulation. In SMG tissue neuronal NE uptake, release, synthesis and endogenous content were determined. In addition phosphoinositide intracellular signaling was also investigated. RESULTS: CSA administration caused an increase in salivary secretion evoked by methoxamine (alpha-adrenergic agonist) and NE but failed to modify salivation evoked by beta-adrenergic stimulation (isoproterenol). Long-term CSA administration decreased NE release and synthesis whereas it enhanced the amine uptake and phosphoinositide hydrolysis in the SMG. CONCLUSIONS: The administration of CSA for 30 days induced salivary gland sensitization likely mediated by diminished adrenergic input. Present results suggest that the decreased sympathetic activity evoked by long-term CSA administration in the rat SMG may lead to sensitization of the gland supported by increased phosphoinositide hydrolysis and enhanced adrenergic-evoked salivation.

Centrally applied atrial natriuretic factor diminishes bile secretion in the rat.

Little is known about the role of centrally applied peptides in the regulation of bile secretion. We previously reported that the intravenous injection of atrial natriuretic factor (ANF) reduces bile acid dependent flow without affecting portal venous pressure in the rat. In the present work, we studied the effects of centrally applied ANF on bile secretion and the possible pathways involved. Rats were cannulated in the brain lateral ventricle for the administration of 1, 10 and 100 ng/microl ANF. After 1 week, the common bile duct was cannulated and bile samples were collected every 15 min for 60 min after the administration of ANF. The excretion rate of various biliary components was assessed. Bile secretion experiments were also performed after bilateral truncal vagotomy or atropine administration to evaluate the participation of a vagal pathway. In addition, the role of the sympathetic system was addressed by combined administration of propranolol and phentolamine. Centrally applied ANF did not modify blood pressure but diminished bile flow and bile acid output. It also reduced sodium and potassium secretion but did not modify protein or phospholipid excretion. Neither bilateral truncal vagotomy nor atropine administration abolished ANF response. Furthermore, combined administration of adrenergic antagonists did not alter ANF inhibitory effect on bile flow. In conclusion, centrally applied ANF reduced bile acid dependent flow not through a vagal or adrenergic pathway in the rat, suggesting the involvement of a peptidergic pathway.

Modulation of cardiac natriuretic peptide gene expression following endothelin type A receptor blockade in renovascular hypertension.

OBJECTIVE: Increased expression of the cardiac natriuretic peptides (NP), atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) is observed during chronic hemodynamic overload. The mechanisms underlying this process are not fully understood. In vitro, endothelin 1 (ET-1) is a powerful stimulator of cardiac NP and, therefore, has been assumed to be one possible mediator of increased NP gene expression following chronic pressure or volume overload. In the present work we investigated the possible role of ET-1 in mediating the observed upregulation of cardiac NP in two kidney-one clip (2K-1C) Goldblatt hypertensive rats treated for 6 weeks with the ET-1 type A (ET(A)) receptor subtype receptor antagonist ABT-627. METHODS: 2K-1C hypertension was induced in male Sprague-Dawley rats weighing 100-125 g by placing a silver clip (internal diameter 0.25 mm) around the left renal artery through a flank incision. The right kidney was left undisturbed. Sham operated rats underwent the same experimental procedures but no clip was placed on the left renal artery. ABT-627 was administered (10 mg/kg per day) in the drinking water for 6 weeks. RESULTS: In hypertensive rats, ABT-627 prevented a further rise in blood pressure beginning at 3 weeks after clipping and reduced the ventricular hypertrophy observed at the end of the experiment. ET(A) blockade prevented enhanced NP gene expression in the right ventricle and partially prevented it in the left ventricle. No modifications in atrial NP gene expression were observed in either control or 2K-1C animals. ET(A) blockade decreased BNP circulating levels but did not affect ANF plasma levels in clipped rats. ABT-627 increased alpha-myosin heavy chain gene expression and decreased the abundance of the beta isoform transcript. CONCLUSION: The results obtained in the present investigation show the participation of ET-1 in the increased expression of ventricular NP in 2K-1C renovascular hypertension and an apparent lack of effect of ET(A) blockade on atrial NP gene expression in both control and hypertensive animals thus showing that in vivo, atrial and ventricular NP gene expression are differentially regulated.

AT-1 receptor and phospholipase C are involved in angiotensin III modulation of hypothalamic noradrenergic transmission.

1. We previously reported that angiotensin III modulates noradrenergic neurotransmission in the hypothalamus of the rat. In the present work we studied the effects of angiotensin III on norepinephrine release and tyrosine hydroxylase activity. We also investigated the receptors and intracellular pathways involved in angiotensin III modulation of noradrenergic transmission. 2. In rat hypothalamic tissue labeled with [3H]norepinephrine 1, 10, and 100 nM and 1 microM losartan (AT1 receptor antagonist) had no effect on basal neuronal norepinephrine release, whereas 10 and 100 nM and 1 microM losartan partially diminished norepinephrine secretion evoked by 25 mM KCl. The AT2 receptor antagonist PD 123319 showed no effect either on basal or evoked norepinephrine release. The increase in both basal and evoked norepinephrine output induced by 1 microM angiotensin III was blocked by 1 microM losartan, but not by 1 microM PD 123319. 3. The phospholipase C inhibitor 5 microM neomicin inhibited the increase in basal and evoked norepinephrine release produced by 1 microM angiotensin III. 4. Tyrosine hydroxylase activity was increased by 1 microM angiotensin III and this effect was blocked by 1 microM LST and 5 microM neomicin, but not by PD 123319. On the other hand, 1 microM angiotensin III enhanced phosphatidyl inositol hydrolysis that was blocked by 1 microM losartan and 5 microM neomicin. PD 123319 (1 microM) did not affect ANG III-induced phosphatidyl inositol hydrolysis enhancement. 5. Our results confirm that angiotensin III acts as a modulator of noradrenergic transmission at the hypothalamic level through the AT1-phospholipase C pathway. This enhancement of hypothalamic noradrenergic activity suggests that angiotensin III may act as a central modulator of several biological processes regulated at this level by catecholamines, such as cardiovascular, endocrine, and autonomic functions as well as water and saline homeostasis.

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.

Effect of selective ET(A) receptor blockade on natriuretic peptide gene expression in DOCA-salt hypertension.

To determine the role of endothelin-1 (ET-1) in the upregulation of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) observed in deoxycorticosterone acetate (DOCA)-salt hypertension, the selective ET-1 type-A receptor (ET(A)) antagonist ABT-627 was chronically administered to normal controls and hypertensive rats. Chronic ET(A) blockade in DOCA-salt-treated rats prevented the increase in blood pressure and circulating natriuretic protein (NP) levels and partially prevented left ventricular hypertrophy. The changes observed in NP gene expression in the atria were not affected by ABT-627. In the ventricles, ABT-627 reduced NP gene expression. Rats receiving the ET(A) antagonist alone showed reduced left ventricular NP gene expression. ABT-627 did not affect ventricular collagen III gene expression but enhanced left ventricular alpha-myosin heavy chain expression. These findings suggest that in vivo, ventricular but not atrial NP production is regulated by ET-1. This difference in response between atrial and ventricular NP gene expression to ET(A) receptor blockade is similar to that observed by us after applying angiotensin-converting enzyme inhibitors in other hypertensive models. In general therefore, atrial NP gene expression may not be as sensitive to the endocrine environment as is ventricular NP gene expression.

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.

Norepinephrine uptake modifications in circumventricular organs, pons and myelencephalic areas and nuclei in prehepatic portal hypertensive rats.

Peripheral noradrenergic activity is enhanced in portal hypertension and correlates with the progression of the disease. However, little is known about the status of central norepinephrine (NE) in portal hypertension. The aim of the present work was to study the uptake of NE in several areas rich in NE in experimental prehepatic portal hypertension. The experiments were performed in vitro in several encephalic areas and nuclei, obtained according to the 'punch-out technique'. Results showed that in portal hypertensive rats NE uptake enhanced in all areas and nuclei studies (subfornical organ, organum vasculosum lamina terminalis, area postrema, locus coeruleus and nucleus tractus solitarius). The present results suggest that these encephalic areas and brainstem nuclei may be related to the development and/or maintenance of portal hypertension in this animal model.

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.

Atrial natriuretic factor does not affect norepinephrine catabolism in rat hypothalamus and adrenal medulla.

We have previously reported that atrial natriuretic factor (ANF) increases neuronal uptake and endogenous content of norepinephrine (NE) and diminishes neuronal release, synthesis and turn-over of NE in rat hypothalamus and adrenal medulla. The aim of the present work was to study another aspect of NE metabolism and therefore investigate the possible effects of ANF on NE catabolism. The determination of monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) activity and deaminates metabolites formation were studied in vitro in rat hypothalamus and adrenal medulla slices. Results showed that, in the hypothalamus, 100 nM ANF diminished MAO activity while 10 nM ANF did not modify the enzyme activity. Conversely, 10 and 100 nM ANF reduced MAO activity in adrenal medulla. On the other hand, the atrial factor modified neither COMT activity nor the formation of deaminates metabolites in the hypothalamus and adrenal medulla. Present results as well as previous findings support a putative role for ANF in the modulation of NE metabolism not only in the hypothalamus but also in the adrenal medulla of the rat, affecting the storage, release and uptake of NE but not its catabolism.

Atrial natriuretic factor-induced amylase output in the rat parotid gland appears to be mediated by the inositol phosphate pathway.

In previous in vivo studies we have reported that atrial natriuretic factor enhanced induced salivary secretion and increased isoproterenol-induced amylase release in the rat suggesting that, ANF effect could be mediated by phosphatidylinositol hydrolysis. In the present work, the effect of ANF on rat parotid tissue incubated in vitro was investigated with the aim to assess whether the phosphoinositol pathway was involved in ANF intracellular signaling in the parotid gland. Results showed that ANF induced a dose dependent increase in amylase fractional release, which was lower than that evoked by any concentration of isoproterenol. Furthermore 100 nM ANF enhanced isoproterenol-evoked amylase release. The effect of ANF was not affected in the presence of propranolol suggesting the noninvolvement of the beta adrenergic receptor, which is the main stimulus for the output of the enzyme in the parotid gland. However, ANF increased phosphatidylinositol hydrolysis, which implies an increase in intracellular calcium, which is necessary for the achievement of maximal response in amylase release. This effect was abolished in the presence of neomycin supporting ANF direct stimulation of phospholipase C. These results suggest the involvement of the C type natriuretic peptide receptor coupled to phospholipase C in ANF evoked amylase release and ANF enhancement of the isoproterenol-induced output of the enzyme.

Norepinephrine uptake is enhanced in discrete telencephalic and diencephalic areas and nuclei in prehepatic portal hypertensive rats.

Several evidences support the hypothesis that central catecholamines may play a significant role in the production and/or maintenance of different alterations that characterize portal hypertension. The aim of the present work was to study the possible modifications in norepinephrine (NE) metabolism in several telencephalic and diencephalic areas rich in NE in experimental prehepatic portal hypertension. NE uptake was studied as an index of NE metabolism. The experiments were carried out in vitro in encephalic areas and nuclei, obtained according to the punch-out technique. Results indicated that portal hypertensive rats showed an enhancement of NE uptake in olfactory bulb (OB), preoptic area (PA), and supraoptic, periventricular, paraventricular, and arcuate nuclei (SON, PeVN, PaVN, and AN, respectively) compared to sham-operated rats. However, no modifications on NE uptake was observed in the median eminence (ME). Present results suggest that the changes observed in central NE uptake may be related to the development and/or maintenance of the portal hypertensive state.

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.

B and C types natriuretic peptides modify norepinephrine uptake and release in the rat adrenal medulla.

We have previously reported that atrial natriuretic factor (ANF) modulates adrenomedullar norepinephrine (NE) metabolism. On this basis, the aim of the present work was to study the effects of B and C types natriuretic peptides (BNP and CNP) on the uptake, intracellular distribution and release of 3H-NE. Experiments were carried out in rat adrenal medulla slices incubated "in vitro." Results showed that 100 nM of both, CNP and BNP, enhanced total and neuronal NE uptake. Both peptides (100 nM) caused a rapid increase in NE uptake during the first minute, which was sustained for 60 min. NE intracellular distribution was only modified by CNP (100 nM), which increased the granular fraction and decreased the cytosolic pool. On the other hand, spontaneous as well as evoked (KCl) NE release, was decreased by BNP and CNP (50 and 100 nM for spontaneous release and 1, 10, 50 and 100 nM for evoked output). The present results suggest that BNP and CNP may regulate catecholamine secretion and modulate adrenomedullary biological actions mediated by catecholamines, such as blood arterial pressure, smooth muscle tone, and metabolic activities.

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.

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.

Atrial natriuretic factor increases peritoneal dialysis efficiency in nephrectomized rats.

The effect of atrial natriuretic factor (ANF) on peritoneal dialysis was studied in bilaterally nephrectomized rats. ANF was injected prior to every dialysis exchange and blood samples were obtained before the instillation of the dialysis solution and during the collection of dialysates. Urea, creatinine, potassium, and sodium were determined in both plasma and dialysates. Results showed that ANF increased the plasma clearance of all studied solutes, probably through vasodilation. Solute clearances showed a gradual increase with each dialysis exchange in both control and experimental animals. Therefore, ANF plasma levels were assayed before, during, and after peritoneal dialysis in a control group of nephrectomized rats to determine whether ANF plasma levels were modified during dialysis. Plasma ANF values were higher during and after peritoneal dialysis, though basal levels were similar to those of non-nephrectomized rats. These results suggest the release of endogenous ANF from the cardiac atria during peritoneal dialysis. The present results suggest that ANF may be of potential interest in the clinical field to increase the efficiency of peritoneal dialysis in man.