Biomedical subjects

J Gutkowska

Publications and source records attributed to J Gutkowska.

At least 55 records · Page 3Linked to original sources

PubMed1997

ANF system in the newborn piglet pulmonary vessels.

The atrial natriuretic factor (ANF) induces diuresis, natriuresis, and vasodilation. Although it was originally found to be secreted from the atria, ANF synthesis has been demonstrated in other organs. The adult lung is not only the first target organ for ANF, but it also expresses the ANF gene and synthesizes, releases, and clears ANF from the circulation. We have shown the presence of ANF in human fetal lungs and also demonstrated that these lungs can release bioactive ANF. However, the role of the ANF system in the newborn lung is unknown. Therefore we studied the ANF system in pulmonary vessels (arteries and veins dissected from the hilum down to a 100-microm diameter), in isolated perfused lungs, and in the plasma from pulmonary artery and vein of 1- and 7-day-old piglets. High-performance liquid chromatography (HPLC) revealed the presence of both the mature peptide and the ANF prohormone in pulmonary vein microsomes, but in pulmonary arteries, only the mature form was identified. Furthermore, in the veins, the ANF content tended to be higher in 7- than in 1-day-olds. ANF caused a dose-dependent decrease in perfusion pressure (p < 0.05). In veins and arteries, most of the ANF receptors were of the type A guanylate cyclase as opposed to clearance receptors. Interestingly, the ANF receptors were fewer in veins, where synthesis takes place, than in arteries (p < 0.05). Significant circulating ANF plasma levels were measured by radioimmunoassay in both pulmonary artery and vein. However, there was no site difference in ANF plasma levels, suggesting that ANF is cleared and synthesized in the pulmonary vessels. In conclusion, the entire ANF system is present in the newborn piglet pulmonary vessels. The paucity of clearance receptors compared with functional receptors potentiates the role of ANF in the regulation of postnatal pulmonary vascular resistance.

Animals↗

PubMed1997

Atrial natriuretic peptide accounts for increased cGMP in hypoxia-induced hypertensive rat lungs.

Perfusate levels of nitric oxide (NO)-containing compounds and guanosine 3',5'-cyclic monophosphate (cGMP) are increased in hypoxia-induced hypertensive rat lungs. To test if increased cGMP was due to NO stimulation of soluble guanylate cyclase (sGC), we examined effects of inhibition of NO synthase with N omega-nitro-L-arginine (L-NNA) on perfusate accumulation of cGMP in physiological salt solution (PSS)-perfused hypertensive lungs isolated from rats exposed for 3-4 wk to hypobaric hypoxia. Because 200 microM L-NNA did not reduce cGMP, we next examined inhibitors of other pathways of stimulation of either sGC or particulate GC (pGC). Neither 5 microM Zn-protophorphyrin, an inhibitor of CO production by heme oxygenase, nor 10 mM aminotriazole, an inhibitor of H2O2 metabolism by catalase, reduced perfusate cGMP. However, an antiserum to atrial natriuretic peptide (ANP; 100 microliters antiserum/30 ml PSS), to inhibit ANP activation of pGC, completely prevented accumulation of the nucleotide. ANP antiserum was also more effective than L-NNA in reducing lung tissue cGMP. In contrast, L-NNA but not ANP antiserum increased resting vascular tone. These results suggested that whereas ANP determined perfusate and tissue levels of cGMP, NO regulated vascular tone. To test if perfusate cGMP reflected ANP stimulation of pGC in endothelial rather than smooth muscle cells, we examined effects of 10 microM Zaprinast, an inhibitor of cGMP hydrolysis in smooth muscle but not endothelial cells, and found no increase of cGMP in hypertensive lungs. ANP levels were not elevated in hypertensive lungs, and it is unclear by what mechanism the ANP-stimulated activity of pGC is increased in hypertensive pulmonary vascular endothelial cells.

Altitude↗

PubMed1997

Endothelin receptor changes in hypoxia-induced pulmonary hypertension in the newborn piglet.

Endothelin (ET)-1, a potent vasoconstrictor and mitogen, acts through ETA and ETB receptors and may be involved in the pathogenesis of persistent pulmonary hypertension of the newborn. We hypothesized that hypoxia-induced pulmonary hypertension in the newborn is associated with increased ET-1 release and modified ET receptor characteristics leading to vasoconstriction and vascular remodeling. Therefore, we studied 1-day-old piglets exposed for 3 or 14 days to hypoxia (fraction of inspired O2 = 0.10) or normoxia (controls). ET-1 circulating levels in pulmonary artery and vein were measured. Pulmonary vascular reactivity to ET-1 was evaluated using isolated-perfused lungs. ET binding characteristics were examined in microsomes from pulmonary arteries (down to 100 microns). ET-1 circulating levels are low and are not altered by hypoxia. The magnitude of the initial dilator response to ET-1 decreases after 3 days of hypoxia (P < 0.05), whereas the number of ETB receptors is reduced by 40% in the pulmonary arteries (P < 0.05). ETA receptors are predominant (65-90%) in pulmonary arteries. ETA receptors decrease by 50% after 14 days of exposure to hypoxia (P < 0.05), whereas the constrictor response to ET-1 remains unchanged. The fact that the reduction in vasodilator response parallels the decrease in ETB receptors suggests a decrease in receptor expression. We speculate that the maintenance of the vasoconstrictor response to ET-1 despite a reduction in the number of binding sites is likely due to receptor occupancy. In conclusion, in the newborn piglet pulmonary vasculature, ETA and ETB receptors may be affected differently by hypoxia.

Animals↗

PubMed1997

Reduced vasodilator response to ANF in hypoxia-induced pulmonary hypertension in the newborn piglet.

Recent evidence suggests that, in adult animals with hypoxia-induced pulmonary hypertension, atrial natriuretic factor (ANF) may modulate pulmonary vascular tone and may have a protective effect. However, its role in the pathogenesis of pulmonary hypertension of the newborn is unknown. We hypothesized that, in the newborn, hypoxia-induced pulmonary hypertension would result in ANF receptor downregulation, resulting in decreased dilator response, favoring pulmonary vasoconstriction and vascular remodeling. Therefore, we studied, in 1-day-old piglets exposed to hypoxia (fraction of inspired O2 0.10) for 3 or 14 days to induce pulmonary hypertension, 1) ANF release by measuring circulating levels of ANF by radioimmunoassay in pulmonary artery and veins, 2) pulmonary vascular reactivity to ANF using isolated perfused lungs, and 3) binding characteristics by examining the concentration dependence of ANF binding and competitive binding of 125I-labeled ANF with ANF, brain natriuretic peptide, C-type natriuretic peptide, and the specific ligand for ANF clearance receptor on microsomes from pulmonary arteries (down to 100 microns). ANF circulating levels are increased after exposure to hypoxia compared with normoxia, reaching significance at 14 days (P < 0.005). The magnitude of ANF dilator response is diminished after exposure to hypoxia (P < 0.05). Saturation studies reveal that the number of ANF receptors is diminished in hypoxia after 3 days but reaches significance after 14 days (P < 0.01) compared with their respective normoxic control. At either condition, the majority of these receptors are of the functional type, whereas clearance receptors are virtually undectable. These results suggest that hypoxia increases circulating ANF and causes a decreased responsiveness of the pulmonary vasculature to ANF. Receptor down-regulation may explain part of the reduced dilator response, although the involvement of other mechanisms is not excluded.

Animals↗

PubMed1997

Renal alterations of atrial natriuretic peptide receptors by chronic moderate ethanol treatment.

Previous studies have shown that chronic moderate ethanol (EtOH) consumption prevents the age-dependent increase in blood pressure. However, the physiological systems mediating the antihypertensive effects of EtOH are not known. The objective of the present studies was to investigate the effects of chronic (8 mo) moderate EtOH consumption on renal natriuretic receptors of spontaneously hypertensive (SHR) and normotensive (WKY) rats, using competitive binding assay and autoradiographic techniques. In the renal glomeruli, the maximal binding capacity (Bmax) of the heterogeneous atrial natriuretic peptide (ANP) receptor population (NPR-A and NPR-C) was significantly lower in EtOH-treated SHR and WKY rats compared with water-treated controls. Quantification of receptor subtypes showed that this decrease was primarily the result of NPR-C down-regulation. The apparent dissociation constant (Kd) was also decreased by the EtOH treatment. In the renal papilla, the Bmax of the homogeneous receptor population (NPR-A) was significantly elevated by long-term EtOH consumption in both strains compared with water-treated controls. However, the Kd was unaltered by the EtOH administration. Thus EtOH treatment induced specific alterations in renal natriuretic receptors that may play a role in the "protective" effect of moderate EtOH consumption on the age-dependent increase in blood pressure.

Animals↗

PubMed1997

Atrial natriuretic peptide in brain and pituitary gland.

The data reviewed establish the presence and important role in body fluid homeostasis of brain atrial natriuretic peptide (ANP) in all vertebrate-species examined. The peptide is localized in neurons in hypothalamic and brain stem areas involved in body fluid volume and blood pressure regulation, and its receptors are located in regions that contain the peptide. Most, if not all, of the actions of ANP are mediated by activation of particulate guanylyl cyclase with generation of guanosine 3',5'-cyclic monophosphate, which mediates its actions in brain as in the periphery. Although atrial stretch releases ANP from cardiac myocytes, the experiments indicate that the response to acute blood volume expansion is markedly reduced after elimination of neural control. Volume expansion distends baroreceptors in the right atria, carotid-aortic sinuses, and kidney, altering afferent input to the brain stem and hence the hypothalamus, resulting in stimulation via ANPergic neurons in the hypothalamus of oxytocin release from the neurohypophysis that circulates to the right atrium to stimulate ANP release. The ANP circulates to the kidney and induces natriuresis. Atrial natriuretic peptide also induces vasodilation compensating rapidly for increased blood volume by increased vascular capacity. Atrial natriuretic peptide released into hypophysial portal blood vessels inhibits release of adrenocorticotropic hormone (ACTH), thereby decreasing aldosterone release and enhancing natriuresis. Furthermore, the ANP neurons inhibit AVP release leading to diuresis and decreased ACTH release. Activation of hypothalamic ANPergic neurons via volume expansion also inhibits water and salt intake. These inhibitory actions may be partially mediated via ANP neurons in the olfactory system altering salt taste. Atrial natriuretic peptide neurons probably also alter fluid movement in the choroid plexus and in other brain vascular beds. Therefore, brain ANP neurons play an important role in modulating not only intake of body fluids, but their excretion to maintain body fluid homeostasis.

Animals↗

PubMed1997

Role of atrial natriuretic factor, hemodynamic changes and renal nerves in the renal effects of intraperitoneal morphine in conscious rats.

The aim of the present study was to investigate the role of renal nerves and atrial natriuretic factor (ANF) in the mechanisms responsible for the diuresis and antinatriuresis induced by morphine in rats in a normal state of hydration. Male Wistar rats weighing 350-400 g were divided into two groups: one group was subjected to bilateral renal denervation, whereas the other consisted of sham-operated controls. The animals were placed in individual metabolic cages, and morphine (1.25, 2.5, 5.0 or 10.0 mg/kg body weight) or vehicle (0.5 ml isotonic saline) was injected intraperitoneally. Urine was collected hourly for 1 h before and 3 h after morphine injection. The lower doses of morphine (1.25 and 2.5 mg/kg body weight) induced a transient increase in urine output (from 1.17+/-0.12 to 2.49+/-0.34 and from 0.78+/-0.08 to 1.71+/-0.18 microl/min, respectively). The diuretic response to these doses was similar in bilaterally denervated rats. Higher doses (5.0 and 10.0 mg/kg body weight) induced a marked but transient reduction in the urinary flow rate during the first hour (from 0.90+/-0.11 to 0.48+/-0.05 and from 1.37+/-0.17 to 0.45+/-0.08 microl/min, respectively), followed by a delayed diuretic effect. The antidiuretic action of morphine was not observed in bilaterally denervated rats. In control rats, morphine induced a dose-dependent decrease in sodium excretion 1 h after administration, an effect that was blunted in the denervated group. The lower morphine doses (1.25 and 2.5 mg/kg body weight) elicited a transient increase in the glomerular filtration rate (GFR) in both control (from 1.23+/-0.12 to 1.67+/-0.17 and from 1.28+/-0.14 to 2.41+/-0.18 ml/min) and bilaterally denervated rats (from 1.29+/-0.14 to 1.66+/-0.17 and from 1.18+/-0.22 to 1.72+/-0.19 ml/min), whereas the higher doses (5.0 and 10.0 mg/kg body weight) produced a marked, transient GFR decrease in the controls (from 1.25+/-0.11 to 0.43+/-0.05 and from 1.13+/-0.17 to 0.47+/-0.08 ml/min) and bilaterally denervated animals (from 1.48+/-0.16 to 0.74+/-0.09 and from 1.22+/-0.15 to 0.73+/-0.06 ml/min), although the reduction was less pronounced with renal denervation. Morphine induced a transient, dose-dependent reduction in blood pressure (from 114+/-1 to 71+/-6 mm Hg at 10.0 mg/kg body weight) and a dose-dependent elevation of plasma ANF. No differences in plasma ANF were observed between control and denervated animals under basal conditions (60+/-7 vs. 42+/-6 pg/ml) or after injection of 2.5 or 5.0 mg/kg of morphine (155+/-11 vs. 167+/-9 and 360+/-9 vs. 401+/-9 pg/ml, respectively). Our data suggest that the renal responses to intraperitoneal morphine administration derive from the integration of several different actions: (1) increased ANF release; (2) decreased arterial pressure; (3) subsequent activation of renal sympathetic activity, and (4) the direct effect of morphine on tubular function.

Analgesics, Opioid↗

PubMed1997

Clonidine and ST-91 may activate imidazoline binding sites in the heart to release atrial natriuretic peptide.

It is well established that the antihypertensive drug clonidine acts through specific imidazoline receptors in the brain and kidney to increase diuresis, natriuresis, and kaliuresis. We have previously shown that the effects of clonidine are associated with elevated plasma atrial natriuretic peptide (ANP). Similar to clonidine, ST-91, a clonidine analogue that does not cross the blood-brain barrier, evokes renal responses that are also associated with elevated plasma ANP. The mechanisms of ANP increase elicited by these imidazoline drugs are unclear. Since ANP is primarily released from the cardiac atria, we investigated the direct effect of the imidazoline drugs on ANP release by incubating left and right atrial sections with 10(-6) mol/L ST-91 in the presence and absence of efaroxan, a selective imidazoline I1 receptor antagonist, for 30 minutes at 37 degrees C. ST-91 significantly stimulated ANP release, and the effect was inhibited by 10(-6) mol/L efaroxan. Further studies using heart perfusion with the imidazoline drugs with and without antagonists over 30 minutes revealed that both clonidine and ST-91 gradually stimulated ANP release. Also, perfusion with these compounds resulted in a gradual decrease in heart rate, but bradycardia was significant only with clonidine. The effects of ST-91 were inhibited by 10(-6) mol/L efaroxan and to a lesser extent by 10(-6) mol/L yohimbine, implying that the actions of ST-91 were mainly mediated by I1 receptors. On the other hand, the actions of clonidine were inhibited by 10(-5) mol/L efaroxan and by 10(-6) mol/L yohimbine, an alpha2-adrenoceptor antagonist, which may suggest that the actions of clonidine were preferentially mediated by alpha2-adrenoceptors in the heart. These results indicate that the peripheral actions of clonidine are probably mediated by alpha2 and imidazoline receptors and may involve direct stimulation of ANP release by the cardiac atria--an effect that may account for the increase in plasma ANP levels and diuresis and natriuresis observed in vivo after administration of clonidine and its analogues.

Adrenergic alpha-Agonists↗

PubMed1997

Correlations between ANP concentrations in atria, plasma and cerebral structures and sodium chloride preference in Wistar rats.

We determined whether ANP (atrial natriuretic peptide) concentrations, measured by radioimmunoassay, in the ANPergic cerebral regions involved in regulation of sodium intake and excretion and pituitary glad correlated with differences in sodium preference among 40 Wistar male rats (180-220 g). Sodium preference was measured as mean spontaneous ingestion of 1.5% NaCl solution during a test period of 12 days. The relevant tissues included the olfactory bulb (OB), the posterior and anterior lobes of the pituitary gland (PP and AP, respectively), the median eminence (ME), the medial basal hypothalamus (MBH), and the region anteroventral to the third ventricle (AV3V). We also measured ANP content in the right (RA) and left atrium (LA) and plasma. The concentrations of ANP in the OB and the AP were correlated with sodium ingestion during the preceding 24 h, since an increase of ANP in these structures was associated with a reduced ingestion and vice-versa (OB: r = -0.3649, P < 0.05; AP: r = -0.3291, P < 0.05). Moreover, the AP exhibited a correlation between ANP concentration and mean NaCl intake (r = -0.4165, P < 0.05), but this was not the case for the OB (r = 0.2422). This suggests that differences in sodium preference among individual male rats can be related to variations of AP ANP level. Earlier studies indicated that the OB is involved in the control of NaCl ingestion. Our data suggests that the OB ANP level may play a role mainly in day-to-day variations of sodium ingestion in the individual rat.

Animals↗

PubMed1997

Neuroendocrine regulation of salt and water metabolism.

Neurons which release atrial natriuretic peptide (ANPergic neurons) have their cell bodies in the paraventricular nucleus and in a region extending rostrally and ventrally to the anteroventral third ventricular (AV3V) region with axons which project to the median eminence and neural lobe of the pituitary gland. These neurons act to inhibit water and salt intake by blocking the action of angiotensin II. They also act, after their release into hypophyseal portal vessels, to inhibit stress-induced ACTH release, to augment prolactin release, and to inhibit the release of LHRH and growth hormone-releasing hormone. Stimulation of neurons in the AV3V region causes natriuresis and an increase in circulating ANP, whereas lesions in the AV3V region and caudally in the median eminence or neural lobe decrease resting ANP release and the response to blood volume expansion. The ANP neurons play a crucial role in blood volume expansion-induced release of ANP and natriuresis since this response can be blocked by intraventricular (3V) injection of antisera directed against the peptide. Blood volume expansion activates baroreceptor input via the carotid, aortic and renal baroreceptors, which provides stimulation of noradrenergic neurons in the locus coeruleus and possibly also serotonergic neurons in the raphe nuclei. These project to the hypothalamus to activate cholinergic neurons which then stimulate the ANPergic neurons. The ANP neurons stimulate the oxytocinergic neurons in the paraventricular and supraoptic nuclei to release oxytocin from the neural lobe which circulates to the atria to stimulate the release of ANP. ANP causes a rapid reduction in effective circulating blood volume by releasing cyclic GMP which dilates peripheral vessels and also acts within the heart to slow its rate and atrial force of contraction. The released ANP circulates to the kidney where it acts through cyclic GMP to produce natriuresis and a return to normal blood volume.

Adrenocorticotropic Hormone↗

PubMed1997

Does plasma ANP participate in natriuresis induced by alpha-MSH?

alpha-Melanocyte-stimulating hormone (alpha-MSH; 0.6 and 3 nmol) micro-injected into the anteroventral region of the third ventricle (AV3V) induced a significant increase in diuresis without modifying natriuresis or kaliuresis. Intraperitoneal (ip) injection of alpha-MSH (3 and 9.6 nmol) induced a significant increase in urinary sodium, potassium and water excretion. Intraperitoneal (3 and 4.8 nmol) or iv (3 and 9.6 nmol) administration of alpha-MSH did not induce any significant changes in plasma atrial natriuretic peptide (ANP), suggesting that the natriuresis, kaliuresis and diuresis induced by the systemic action of alpha-MSH can be dissociated from the increase in plasma ANP. These preliminary results suggest that alpha-MSH may be involved in a gamma-MSH-independent mechanism of regulation of hydromineral metabolism.

Animals↗

PubMed1997

Atrial natriuretic peptide and feeding activity patterns in rats.

This review presents historical data about atrial natriuretic peptide (ANP) from its discovery as an atrial natriuretic factor (ANF) to its role as an atrial natriuretic hormone (ANH). As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A) and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways.

Adrenal Glands↗

PubMed1997

Regulation of the natriuretic peptide system in rat uterus during the estrous cycle.

Uterine natriuretic peptides may be involved in the alterations that occur in the uterus during the estrous cycle through its role in hydromineral balance. The following studies were performed to determine whether uterine natriuretic peptides and receptors follow a cyclic pattern during the estrous cycle. The results obtained show that atrial natriuretic peptide (ANP) content in rat uterine tissue was low in proestrus (8.5 +/- 2.6 pg/g) and significantly increased (P < 0.001) in estrus (71.5 +/- 16.6 pg/g), metestrus (82.6 +/- 19.7 pg/g) and diestrus (91.0 +/- 19.4 pg/g), whereas plasma ANP was not altered during the cycle. Similarly, measurement of uterine ANP mRNA by reverse transcribed polymerase chain reaction (RT-PCR) indicated lowest levels of ANP mRNA at proestrus. Measurement of C-type natriuretic peptide (CNP) by a specific and sensitive radioimmunoassay revealed that uterine CNP also varies with the estrous cycle. Uterine CNP was low in diestrus (143.2 +/- 22.4 pg/mg protein) as compared with proestrus, estrus and metestrus (305.3 +/- 51.5, 267.5 +/- 44.9, 291 +/- 41.2 pg/mg protein respectively, P < 0.05). Autoradiography performed on uterine tissue slices localized natriuretic peptide receptors to myometrial smooth muscle layers and to endometrial uterine glands. High binding of 125I-ANP was observed in proestrus and estrus with 60-75% decreases during metestrus and diestrus. Binding of 125I-tyr0CNP to uterine slices was also high during proestrus, but declined by 35% at estrus, metestrus and diestrus. The alterations in the receptors were also observed at the level of synthesis. RT-PCR detection of guanylyl cyclase A (GC-A) receptor mRNA and guanylyl cyclase B (GC-B) mRNA showed high signals at proestrus but 4- and 2-fold reductions respectively at metestrus and diestrus. In conclusion, variations in uterine ANP and CNP and their receptors during the rat estrous cycle imply the involvement of the natriuretic peptides in uterine hydromineral balance and myometrial motor activity.

Animals↗

PubMed1997

Increased plasma atrial natriuretic peptide after ingestion of low doses of ethanol in humans.

Previous studies have demonstrated that, in human, acute consumption of high doses of ethanol, administered in a large quantity of fluid, with or without volume-loading, induced either a decrease or an increase in the plasma content of atrial natriuretic peptide (ANP)--a substance that has a hypotensive effect. The objective of the present study was to examine the effect of low doses of ethanol (0, 0.25, and 0.50 g of ethanol/kg of body weight) administered to six normotensive individuals, in a small volume of fluid without prior volume-loading. Before and at various intervals after administration of the placebo or ethanol drinks, heart rate and blood pressure were measured and blood samples were taken for estimation of the plasma ANP, arginine vasopressin, and cortisol contents. Results indicated small changes in blood pressure and heart rate after ingestion of either the placebo or ethanol drinks. On the other hand, a significant increase in the plasma ANP content was observed at 15 min after ingestion of both the 0.25 and 0.50 g of ethanol/kg of body weight doses, but not after the placebo drink. Plasma ANP levels were still elevated at 45 min postethanol intake, but had returned to basal levels at 120 min after the ethanol drink. Interestingly, it was noticed that the higher dose of ethanol (0.50 g) did not induce a higher plasma ANP concentration than the lower dose (0.25 g) of ethanol; however, the plasma ANP content remained elevated for a longer period. Furthermore, the increase in plasma ANP content was not due to ethanol or stress-induced increases in the plasma arginine vasopressin and cortisol contents, because the plasma concentration of these hormones remained either at basal or below basal levels for the duration of the experiment. In conclusion, ingestion of low amounts of ethanol equivalent to 1 or 2 standard drinks induced an increase in plasma ANP content.

Adult↗

PubMed1997

The peripheral action of clonidine analog ST-91: involvement of atrial natriuretic factor.

It is generally thought that the cardiovascular and renal effects of clonidine, an alpha-2 adrenergic agonist, are mediated by central mechanisms. Our previous work has shown that diuresis and natriuresis caused by central administration of clonidine are mediated by an enhanced release of atrial natriuretic factor (ANF). Because clonidine has been shown to have peripheral actions the objective of the present study was to determine whether ANF is also involved in these actions. Studies were performed with use of a structural clonidine analog, ST-91, which does not cross the blood-brain barrier, Intravenous injection of various doses (0-250 micrograms/rat) of ST-91 into conscious, normally hydrated female Sprague-Dawley rats (200-250 g) produced dose-related increases in urinary output, which were accompanied by significant increases in urinary sodium, potassium and cGMP excretion. Compared with saline, the highest dose of ST-91 (250 micrograms/rat) during the first hour of treatment significantly (P < .001, n = 18) enhanced urinary output (0.2 +/- 0.1 vs. 3.0 +/- 1.1 ml/h) and excretion of sodium (28 +/- 4 vs. 345 +/- 50 mumol/h), potassium (10 +/- 4 vs. 165 +/- 37 mumol/h) and cGMP (191 +/- 29 vs. 1340 +/- 322 pmol/h), the biological marker of ANF. These renal responses were associated with increased plasma ANF (59 +/- 7 vs. 810 +/- 28 pg/ml, P < .001, n = 12), measured 10 min after ST-91 (250 micrograms/rat), which remained elevated for at least 1 h (P < .01, n = 6). The enhanced renal responses that were induced by 10 micrograms ST-91 were partially, yet significantly inhibited by yohimbine (50 micrograms), an alpha-2 antagonist. On the other hand, efaroxan (500 micrograms), an l1 imidazoline receptor antagonist, showed a stronger inhibitory effect, whereas naloxone (0.8 mg) had no effect. Pretreatment of rats with anti-ANF reduced the diuretic and natriuretic effects of ST-91. These results indicate that the renal effects of ST-91 are mediated by imidazoline as well as by alpha-2 adrenergic receptors, but not by opioid receptors. Furthermore, the renal effects evoked by ST-91 are mediated by ANF.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1997

[Effect of surgical treatment of otitis media with effusion on children. Personal experience].

The authors present their observations upon surgically treated children with otitis media with effusion. The results are indicative of usefulness of ventilation tubes, myringotomy and adenoidectomy in the treatment of the otitis media with effusion in children. The efficiency of the treatment is based on the hearing examination and tympanometry, and the lack of recurrence of inflammation of the middle ear. 67.6% of cases revealed normal hearing.

Child↗

PubMed1996

Effect of chronic moderate ethanol consumption on heart brain natriuretic peptide.

There is experimental evidence indicating that chronic moderate ethanol consumption delays the age-dependent increase in blood pressure. Since the brain natriuretic peptide (BNP) is a potent hypotensive hormone, the effect of chronic ethanol treatment on the heart BNP system was investigated, using spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Chronic moderate ethanol consumption resulted in significantly lower circulating BNP levels for both SHR (206.9 +/- 18.5 vs. 306.9 +/- 28.1 pg/ml, n = 12, P < or = 0.05) and WKY rats (131.3 +/- 20.7 vs. 220.6 +/- 25.0 pg/ml, n = 12, P < or = 0.05). Left and right atrial BNP content and concentration in WKY rats and left atrial BNP content and concentration in SHR rats were augmented by the ethanol treatment, but not atrial BNP mRNA. In ventricular tissue, alcohol had no effect on total BNP content of either SHR or WKY rats, but it induced a significant elevation in ventricular BNP concentration (microgram/mg protein) and BNP mRNA in SHR, but not WKY rats. Thus, chronic ethanol treatment resulted in specific alterations in the activity of the heart BNP system.

Age Factors↗

PubMed1996

Natriuretic peptide system in the rat submaxillary gland.

Natriuretic peptides and their receptors were characterized in rat submaxillary glands (SGs). Reverse phase-high performance liquid chromatography (HPLC) of rat SGs extracts revealed the presence of the 28-amino-acid (AA) circulating peptide ANP (Ser99-Tyr126) and the 126-AA prohormone (Asn1-Tyr126). The presence of ANP prohormone indicated that SGs are a site of ANP synthesis. Indeed, ANP mRNAs were demonstrated. ANP mRNA was 10 times lower than in the lung and only about 7 times lower than in the hypothalamus. ANP content in SG was determined as 30 +/- 8 ng/mg of protein (n = 7). In addition the presence of another member of the natriuretic peptide family, C-type natriuretic peptide (CNP), was found in SG. The CNP level of 293 +/- 38 pg/mg protein was significantly higher than in the lungs (44 +/- 6 pg/mg protein, P < 0.001, n = 5), but about 15 times lower than in hypothalamus (4.5 +/- 0.6 ng/mg protein, P < 0.001, n = 6). Both guanylyl cyclase and clearance receptors were expressed in SG. The presence of natriuretic peptide transcripts and their receptors suggests a role in rat SG functions.

Animals↗