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Biomedical subjects

J Gutkowska

Publications and source records attributed to J Gutkowska.

At least 109 records · Page 6Linked to original sources
PubMed1993

Possible role of endothelin acting within the hypothalamus to induce the release of atrial natriuretic peptide and natriuresis.

Since endothelin has been localized in neurons in areas involved in water and electrolyte metabolism, areas which also contain atrial natriuretic peptide (ANP) neurons, we determined whether endothelin would release ANP and induce natriuresis. Endothelin-3 (ET-3) in doses ranging from 38 to 760 pmol was microinjected into the third ventricle (3V) of conscious, water-loaded male rats, and the effect on natriuresis and plasma ANP was determined. ET-3 evoked a dose-related natriuresis beginning within 20 min of injection. Even the lowest dose tested (38 pmol) was effective. At a dose of 95 pmol, it produced a rapid increase of plasma ANP within 5 min peaking at 20 min. A slight kaliuresis and antidiuresis was observed at the 2 highest doses of 380 and 760 pmol. The urinary changes following 3V injection of ET-3 were similar to those evoked by ANP, except for the antidiuresis with increased sodium concentration which followed injection of the 2 higher doses. These results suggest that these 2 higher doses also released vasopressin. Alternatively, activation of the sympathetic nervous system by these higher doses may have decreased glomerular filtration rate and been in part responsible for the antidiuresis. The results with 3V injection of ET-3 contrasted sharply with those obtained following intravenous injection of the 95-pmol dose injected intraventricularly. This intravenous dose of ANP induced a transient decrease in sodium and potassium excretion and urine volume, maximal at 20 min, and had no effect on plasma ANP concentrations at 5 or 20 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The atrial natriuretic peptide system in rat ovaries.

The atrial natriuretic peptide (ANP) gene is expressed in several extracardiac tissues where ANP is thought to be involved in autocrine or paracrine regulation. The current studies were designed to characterize the ANP system in rat ovaries. ANP content in rat ovaries was estimated by RIA to be 240 +/- 70 pg/mg protein. HPLC revealed the presence of the 28-amino acid circulating peptide as well as the 126-amino acid prohormone, suggesting that the ovaries are a site of ANP synthesis. Indeed, ANP messenger RNA was detected in this tissue by RNase mapping. ANP present in ovarian extracts displaced [125I]ANP from bovine adrenal receptors (R1 class) in a dose-dependent manner and in parallel to the synthetic peptide, indicating that it possesses biological activity. Immunocytochemical studies localized ANP to interstitial cells surrounding the follicles; weaker but specific staining was also observed in the ovum. High affinity ANP receptors (dissociation constant, 0.30 +/- 0.06 nM; maximum binding capacity, 160 +/- 40 fmol/mg protein) were identified in ovarian membranes. Unlabeled ANP but not c-atrial natriuretic factor (a specific agonist of ANP clearance receptors) competed with binding of [125I]ANP to ovarian membranes in a dose-dependent manner, suggesting that ovarian ANP receptors are predominantly of the R1 class. This was confirmed by cross-linking studies with [125I]ANP, which detected a single protein band with a molecular size of about 120 kilodaltons, corresponding to that of the guanylate cyclase-coupled R1 class of receptor. Consistent with the presence of biologically active receptors, ANP markedly enhanced cGMP accumulation (by 15-fold) in ovarian cells. The presence of both local ANP synthesis and high affinity transducing receptors in the ovaries indicates that the peptide plays a local role in ovarian growth or steroidogenesis.

Adrenal Glands↗
PubMed1992

Carotid-aortic and renal baroreceptors mediate the atrial natriuretic peptide release induced by blood volume expansion.

Our previous studies have shown that stimulation of the anteroventral third ventricle (AV3V) region of the brain increases atrial natriuretic peptide (ANP) release, whereas lesions of the AV3V region or median eminence of the tuber cinereum block the release of ANP caused by blood volume expansion. These results suggest that participation of the central nervous system is critical to this response. The role of baroreceptors in the response was evaluated in the current research by studying the response of plasma ANP to blood volume expansion induced by intravenous injection of hypertonic saline solution (0.3 M NaCl, 2 ml/100 g of body weight, over 1 min) in conscious, freely moving male rats. Plasma samples were assayed for ANP by radioimmunoassay. In sham-operated rats, blood volume expansion induced a rapid increase in plasma ANP: the concentration peaked at 5 min and remained elevated at 15 min after saline injection. One week after deafferentation of the carotid-aortic baroreceptors, basal plasma ANP concentrations were highly significantly decreased on comparison with values of sham-operated rats; plasma ANP levels 5 min after blood volume expansion in the deafferented rats were greatly reduced. Unilateral right vagotomy reduced resting levels of plasma ANP but not the response to blood volume expansion; resting concentrations of plasma ANP and responses to expansion were normal in bilaterally vagotomized rats. In rats that had undergone renal deafferentation, resting levels of ANP were normal but the response to blood volume expansion was significantly suppressed. The evidence indicates that afferent impulses via the right vagus nerve may be important under basal conditions, but they are not required for the ANP release induced by blood volume expansion. In contrast, baroreceptor impulses from the carotid-aortic sinus regions and the kidney are important pathways involved in the neuroendocrine control of ANP release. The evidence from these experiments and our previous stimulation and lesion studies indicates that the ANP release in response to volume expansion is mediated by afferent baroreceptor input to the AV3V region, which mediates the increased ANP release via activation of the hypothalamic ANP neuronal system.

Afferent Pathways↗
PubMed1992

Modulation of arterial endothelin-1 receptors following chronic increases in blood flow.

Experiments were designed to determine whether or not increased contractions to endothelin-1 (ET-1) in arteries chronically exposed to increased blood flow were due to a change in the subtype, number, or affinity of ET receptors on the smooth muscle. A fistula was created between one femoral artery and vein in dogs; contralateral blood vessels were operated as shams. After 6 weeks, the femoral arteries were removed. In both fistula- and sham-operated arteries suspended for the measurement of isometric force in organ chambers, the contractile potency was ET-1 > ET-2 > ET-3. Specific binding of [125I]ET-1 as a function of membrane protein was significantly greater in fistula compared to sham-operated arteries (Bmax = 184.8 +/- 35.9 and 117.4 +/- 25.6 fmol/mg, n = 6, respectively). Affinity of binding was the same in each group of arteries. These results suggest that ETA receptors mediate contraction on canine femoral arterial smooth muscle. These receptors may be upregulated when the artery is exposed chronically to increased blood flow.

Animals↗
PubMed1991

Vitamin D receptors in heart: effects on atrial natriuretic factor.

We report that receptors for vitamin D exist in distinct regions of the heart in female and male mice, predominantly in the right atrium where most of the cardial atrial natriuretic peptide (ANF) is produced. Tritiated 1,25-dihydroxyvitamin D3 (1,25-D3, vitamin D, soltriol) and ANF are colocalized in nuclei and cytoplasm respectively in identical cardiomyocytes. Changes of ANF tissue and blood levels under dietary deficiency and treatment with 1,25-D3 suggest direct genomic actions of vitamin D on myoendocrine cells of the atrium for the regulation of ANF manufacture and secretion. These results were obtained by combining thaw-mount autoradiography with immunocytochemistry using tritiated 1,25-D3 and an antibody against rat ANF. This antibody was also used in a radioimmunoassay to determine atrial natriuretic factor in plasma, atria and ventricles of normal or vitamin D-deficient mice.

Animals↗
PubMed1991

The presence of atrial-natriuretic-factor receptors of ANF-R2 subtype in rat platelets. Coupling to adenylate cyclase/cyclic AMP signal-transduction system.

The effect of atrial natriuretic factor (ANF) on adenylate cyclase activity was studied in rat platelet membranes. ANF-(99-126)-, -(101-126)-, -(103-126)- and -(103-123)-peptide inhibited adenylate cyclase activity in a concentration-dependent manner with an order of potency of ANF-(103-123)-peptide greater than ANF-(99-126)-peptide greater than ANF-(101-126)-peptide greater than ANF-(103-126)-peptide. ANF-(103-123)-peptide and ANF-(99-126)-peptide inhibited the enzyme activity by about 50-55%, with an apparent Ki between 0.1 and 0.5 nM, and ANF-(101-126)-peptide inhibited the enzyme activity by about 35%, with an apparent Ki between 1 and 3 nM. On the other hand, ANF-(103-126)-peptide was the least potent and inhibited the adenylate cyclase activity by about 30% (Ki approximately 10 nM). The inhibitory effect of ANF on adenylate cyclase was also dependent on the presence of guanine nucleotides and was attenuated by amiloride and pertussis toxin. The stimulatory effects of various agonists such as N-ethylcarboxamideadenosine, prostaglandin E1, isoprenaline and forskolin on adenylate cyclase were also inhibited by ANF to various extents; however, the stimulations were not completely abolished. In addition, 125I-labelled ANF-(99-126)-peptide bound specifically to rat platelet membranes. The binding of 125I-ANF was competitively inhibited in a concentration-dependent manner by the unlabelled peptides which were used for adenylate cyclase inhibition. ANF-(103-123)-peptide, ANF-(99-126)-peptide and ANF-(101-126)-peptide were almost equipotent [IC50 (median inhibitory concentration) = 0.1-1 nM], and ANF-(103-126)-peptide was the least potent (IC50 approximately 10 nM). Scatchard analysis of the data revealed the presence of a single class of binding sites of high affinity (Kd approximately 120 pM). Affinity cross-linking of 125I-ANF-(99-126)-peptide to its binding sites in rat platelet membranes and analysis by SDS/PAGE followed by autoradiography showed a predominant labelling of a protein band with an apparent Mr of 66,000. These data indicate the presence of only ANF-R2 (low-Mr) receptors in platelets and suggest that these receptors may be coupled to the adenylate cyclase system.

Adenylate Cyclase Toxin↗
PubMed1991

Lesions of the hypothalamus and pituitary inhibit volume-expansion-induced release of atrial natriuretic peptide.

Expansion of the blood volume causes a release of atrial natriuretic peptide (ANP) that is believed to be important in induction of the subsequent natriuresis and diuresis which, in turn, acts to reduce the increase in blood volume. Since stimulation of the anteroventral portion of the third cerebral ventricle (AV3V) induced a rapid elevation of plasma ANP, whereas lesions of the AV3V were followed by a marked decline in plasma concentration of the peptide, we hypothesized that release of ANP from the brain ANP neuronal system might be important to the control of plasma ANP. The perikarya of the ANP-containing neurons are densely distributed in the AV3V and their axons project to the median eminence and neural lobe. To test the hypothesis that these neurons are involved in volume-expansion-induced ANP release, by using electrolysis we destroyed the AV3V, the site of the perikarya, in male rats. Other lesions were made in the median eminence and posterior pituitary, sites of termination of the axons of these neurons, and also hypophysectomy was performed in other animals. In conscious freely moving animals, volume expansion and stimulation of postulated sodium receptors in the hypothalamus were induced by injection of hypertonic NaCl solution [0.5 or 0.3 M NaCl; 2 ml/100 g (body weight)]. Volume expansion alone was induced with the same volume of an isotonic solution (NaCl or glucose). In the sham-operated rats, volume expansion with hypertonic or isotonic solutions caused equivalent rapid increases in plasma ANP that peaked at 5 min and returned nearly to control values by 15 min. Lesions caused a decrease in the initial levels of plasma ANP on comparison with values from the sham-operated rats, and each type of lesion induced a highly significant suppression of the response to volume expansion on testing 1-5 days after lesions were made. Because a common denominator of the lesions was elimination of the brain ANP neuronal system, these results suggest that the brain ANP plays an important role in the mediation of the release of ANP that occurs after volume expansion. Since the content of ANP in this system is much less than that in the atria, there must be a remarkable increase in synthesis and release of brain ANP associated with this stimulus. It is also possible that blockade of volume-expansion-induced release of other neurohypophyseal hormones, such as endothelin, may block release of ANP from atrial myocytes. It is probable that volume expansion detected by stretch of atrial and carotid-aortic baroreceptors causes afferent input to the brain ANP system, thereby causing increased release of the peptide from the median eminence and neural lobe. Our results emphasize the importance of brain ANP to the control of ANP release to the blood.

Animals↗
PubMed1991

Experimental glaucoma significantly decreases atrial natriuretic factor (ANF) receptors in the ciliary processes of the rabbit eye.

ANF binding sites were analysed in the ciliary processes of rabbits with unilateral experimental glaucoma which had been induced by injecting alpha-chymotrypsin into the posterior chamber of the right eyes. The intraocular pressure (IOP) of glaucomatous eyes was significantly greater (28.4 +/- 4 mmHg) than that of normotensive control eyes (13.1 +/- 1.4 mmHg, mean +/- S.E.M., n = 23, P less than 0.05). ANF concentrations in aqueous humour and the ciliary processes were significantly higher in glaucomatous eyes (91 +/- 2 pg ml-1 and 30.4 +/- 4.2 pg g-1 wet weight) than in normal eyes (3.1 +/- 2.2 pg ml-1 and 10.2 +/- 2.7 pg g-1 wet weight, respectively, n = 6, P less than 0.01). The number of ANF-binding sites (Bmax) in the ciliary processes of glaucomatous rabbit eyes was significantly decreased in comparison to the controls (24 +/- 4 vs. 13 +/- 3 fmol mg-1 protein, n = 10, P less than 0.05). These data suggest that ANF receptors in the ciliary processes are down-regulated and that ANF may play an important role in the pathophysiology of experimental glaucoma.

Animals↗
PubMed1991

Comparative endocrinological and clinical effects of percutaneous estradiol and oral conjugated estrogens as replacement therapy in menopausal women.

Sixty-three healthy post-menopausal women participated in the study aimed at determining the efficiency of percutaneous administration of estradiol (E2) giving physiological plasma levels of the estrogen to provide an efficient relief of climacteric and urogenital symptoms. Among these women, 31 had previous hysterectomy and were randomly allocated to one of the two estrogen replacement therapies while, similarly, the 32 women having an uterus were randomly divided between two groups who received in addition to estrogens, micronized oral progesterone. As estrogen, women received either E2 by percutaneous administration (Oestrogel) or oral conjugated estrogens (Premarin). With Oestrogel, serum E2 and estrone levels were within those seen during premenopause and showed a ratio close to 1.0. Climacteric symptoms were reduced or eliminated similarly in all groups. No changes was noticed on the concentration of serum angiotensinogen with Oestrogel therapy while a 2.5-fold increase was found in women receiving Premarin. As indicated by the 24-week endometrial biopsy, the progestational response induced by oral progesterone at the dose used was sufficient in twenty out of thirty-two women to cause endometrial atrophy, thus suggesting the need for higher amounts of micronized progesterone in a proportion of women. The present data also indicate that Oestrogel provides efficient relief of climacteric and urogenital symptoms without exerting any detectable effect on hepatic function while maintaining the ratio of serum E2/E1 at the physiological value of 1.0.

Administration, Cutaneous↗
PubMed1991

Naloxone effect on ANP in trained and untrained rats.

1. The effect of a dose of naloxone (1 mg.kg-1 b.w.) on peripheral (plasma, atria) and central (hypothalamus, hypophysis) levels of atrial natriuretic peptide (ANP) was investigated in the rat. 2. In control rats, an acute subcutaneous dose of naloxone produced no significant change in plasma ANP, but a decrease (NS) in atrial ANP concentration. 3. In physically conditioned animals, naloxone produced a significant decrease in atrial ANP levels. Receptor sensitivity may thus be involved in this differential response. 4. In hypothalamus and hypophysis, no effect on ANP concentrations was seen after a high dose of naloxone whether in control or in physically conditioned animals, suggesting peripheral and central ANP might be differently regulated, at least after chronic endurance physical training.

Animals↗
PubMed1991

Atrial natriuretic peptide levels in brain venous outflow during cardiopulmonary bypass in humans: evidence for extracardiac hormonal production.

Atrial natriuretic peptide (ANP) is a hormone with an important role in the regulation of extracellular fluid volume. The ANP gene is not only expressed in the heart, but the high concentration of ANP in cardiac blood makes it difficult to demonstrate extraatrial hormonal secretion in vivo. This issue was addressed during complete cardiopulmonary bypass (CPB) in 13 patients undergoing elective cardiac surgery in whom ANP concentrations were followed in the internal jugular vein, representing largely brain venous outflow, as well as a peripheral vein and radial artery, after the heart and lungs were excluded from circulation. Plasma ANP levels in the peripheral venous circulation showed no significant changes during extracorporeal circulation, although they tended to decrease (from 6.75 +/- 2.16 fmol/mL to 4.76 +/- 0.69 fmol/mL; P greater than 0.05). ANP levels in the radial artery decreased significantly after the exclusion of the heart (from 16.84 +/- 3.51 fmol/mL to 6.83 +/- 0.97 fmol/mL; P less than 0.01). In contrast, ANP concentration in the internal jugular vein increased in 12 of 13 patients during the first 15 minutes of CPB (from 9.49 +/- 1.96 fmol/mL to 15.96 +/- 2.8 fmol/mL; P less than 0.01) and remained above the levels found simultaneously in other sampling sites during CPB. High-performance liquid chromatography analysis of plasma extracts showed multiple peaks of ANP, but the elution patterns of peripheral venous blood and brain outflow were similar. One of the immunoreactive peaks was located at the position of standard human ANP (Ser99-Met110-Tyr126).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Atrial natriuretic peptide in patients with acute myocardial infarction without functional heart failure.

The purpose of the present study was to measure plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction without heart failure, and also to assess the temporal sequence of changes of plasma ANP during the first hours of recovery from myocardial infarction. The study was performed in 22 patients who were admitted to the Intensive Care Unit with the diagnosis of acute myocardial ischaemia that had an evolution of less than 6 h. Blood samples were drawn on admission and at 1, 8, and 24 h, and plasma concentrations of ANP, renin, aldosterone, epinephrine, norepinephrine and vasopressin were measured. Compared with control subjects, on admission patients showed increased plasma levels of ANP, as well as increased plasma renin activity (PRA), aldosterone, norepinephrine, epinephrine, dopamine, and antidiuretic hormone (ADH). ANP, but not renin or aldosterone plasma values, decreased with time, and there was a significant correlation between ANP and time after onset of pain. No increase in plasma creatinine was observed during the hospital stay, and the patients showed a negative fluid balance. No relationship was found between the location or extension of the infarction, or morphine treatment and ANP plasma levels. The high levels of ANP seem to counteract the haemodynamic and fluid-retention effects of the vasoconstrictive factors released after myocardial infarction.

Aldosterone↗
PubMed1991

Evidence for atrial natriuretic peptide (ANP) synthesis and the presence of ANP-transducing receptors in the rat olfactory bulb.

This study demonstrates the presence of both atrial natriuretic peptide (ANP) precursor and ANP transcripts in the rat olfactory bulb (OB), a key brain structure involved in the generation of olfaction-dependent behavior. In addition to synthesizing ANP, the OB contains ANP-transducing receptors coupled to the guanylate cyclase system but it is devoid of ANP "clearance receptors." The characterization of biologically active ANP receptors and the evidence for in situ ANP synthesis in this region of the CNS adds credence to the hypothesis that the peptide plays a putative role in olfaction.

Animals↗
PubMed1991

ANF mRNA is detected by the polymerase chain reaction technique in the chorioidea and bodies but not in the retina of the rat eye.

Specific proANF mRNA was demonstrated by the polymerase chain reaction (PCR) technique in ciliary body and chorioidea tissue extracts but not in the retina of the rat eye. However, immunoreactive (IR) ANF was detected in all of these tissues by a specific and sensitive radioimmunoassay (RIA). Since ANF seems to be involved in the maintenance of intraocular pressure, the regulation of ANF gene expression in these distinct eye tissues could be an important factor in the pathogenesis of glaucoma.

Animals↗
PubMed1991

Dissociation of plasma atrial natriuretic peptide responses to upright posture and furosemide administration in patients with normal-, low renin essential hypertension and primary aldosteronism.

Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with normal renin essential hypertension (n = 12), low renin essential hypertension (n = 11) and primary aldosteronism due to aldosterone producing adenoma (APA, n = 8) and idiopathic hyperaldosteronism (IHA, n = 3) after overnight rest in the supine position and after 4 h upright posture and furosemide administration. Plasma renin activity (PRA) and aldosterone (Aldo) levels were also determined. Compared to normal renin essential hypertension (33.6 +/- 2.2 pg/ml), basal plasma ANP was significantly higher in low renin essential hypertension (66.8 +/- 6 pg/ml), IHA (54.1 +/- 6.3 pg/ml) and APA before (62.4 +/- 4.9 pg/ml) but not after adrenal surgery (22 +/- 3 pg/ml). After upright posture and furosemide administration plasma ANP was decreased (p less than 0.01) in patients with low renin and, less markedly, with normal renin essential hypertension, however not in IHA and APA. In about half of the patients with low renin essential hypertension, unchanged PRA after upright posture and furosemide administration was associated with increased plasma Aldo and decreased ANP levels. We conclude that (i) the relatively high basal plasma ANP levels in low renin essential hypertension, IHA and APA may reflect the presence of volume expansion in these patients; (ii) the hormonal responses to upright posture and furosemide administration in patients with normal and low renin essential hypertension may indicate a counterregulatory role of ANP during activation of the renin-angiotensin-aldosterone system; (iii) the high plasma ANP, which is unresponsive to upright posture and furosemide administration, in patients with APA and IHA may be a potentially interesting new finding whose pathophysiological significance remains to be established.

Adult↗
PubMed1991

Molecular forms and biological activity of atrial natriuretic factor in patients with cirrhosis and ascites.

Patients with cirrhosis and ascites show sodium retention and normal or increased plasma levels of atrial natriuretic factor, a peptide with powerful natriuretic activity. To investigate whether this paradoxical observation could be related to a dysregulation in the process of synthesis and maturation of atrial natriuretic factor leading to abnormal molecular forms lacking biological activity, the chromatographic patterns of atrial natriuretic factor contained in plasma extracts from 10 patients with cirrhosis and ascites and 6 healthy subjects were compared. Atrial natriuretic factor from cirrhotic patients was also tested in two different radioreceptor assays, which detect the biologically active form(s) of this peptide. Patients with cirrhosis and ascites had higher plasma levels of atrial natriuretic factor (81.3 +/- 8.5 pg/ml, p less than 0.001) than control subjects (29.8 +/- 3.2 pg/ml). High-performance liquid chromatography analysis of atrial natriuretic factor showed an identical chromatographic pattern in cirrhotic patients and control subjects. Three peaks related to the atrial natriuretic factor prohormone were observed in cirrhotic patients and control subjects, accounting for 64%, 23% and 11% of the total atrial natriuretic factor in cirrhotic patients and 63%, 18% and 8% of the total atrial natriuretic factor in control subjects. The main peak eluted at the same position of synthetic human atrial natriuretic factor (Ser 99-Tyr 126), which represents the major active form of the circulating hormone. Cirrhotic atrial natriuretic factor displayed the same ability to inhibit the binding of 125I-atrial natriuretic factor to rat glomerular and bovine adrenal membrane receptors as synthetic human atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Existence of atrial natriuretic peptide in choroid, retina and ciliary body in rabbits].

The presence of atrial natriuretic factor (ANF) in choroid, retina and ciliary body of rabbit eyes has been studied. The peptide was extracted by reverse phase chromatography using Sep-Pak C18 cartridges. Immunoreactive ANF (Ir-ANF) was measured by a specific RIA. In the choroid, retina and ciliary body the ir-ANF concentrations were 444 +/- 94, 67 +/- 12 and 223 +/- 75 pg/g tissue weight (n = 16), respectively. The biological activity of the acid extract ANF was evaluated by a 125I-ANF binding assay to a retinal particulate preparation. Results demonstrate the existence of biological active ANF in choroid, retina and ciliary body of rabbit eyes. The presence of ANF and its specific receptors in the ocular tissues suggests that this hormone might play a physiological role in the intraocular fluid homeostasis.

Animals↗