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Biomedical subjects

J Gutkowska

Publications and source records attributed to J Gutkowska.

At least 127 records · Page 7Linked to original sources
PubMed1990

Effects of ketanserin on lipids, lipoproteins, and plasma atrial natriuretic factor in patients with essential hypertension.

The effects of ketanserin, 40 mg/day (KE40) and 80 mg/day (KE80) on mean arterial pressure, lipids, lipoproteins, and circulating atrial natriuretic factor (ANF) were investigated in a 24-week controlled study in 29 patients suffering from mild to moderate hypertension. A significant decrease in mean arterial pressure (MAP) was observed after 18 weeks of therapy, accompanied by a 64% (P less than .05) and 80% (P less than .02) increase in circulating ANF levels with KE40 and KE80, respectively. There were no significant changes in mean total cholesterol, triglycerides, or cholesterol of the high density lipoproteins (HDL), low density lipoproteins (LDL), and very low density lipoproteins (VLDL) fractions. There was a significant increase in the mean apo B levels and consequently a slight but statistically significant decrease in the ratio of LDL C/B. It is concluded that both doses of KE are effective for monotherapy of mild to moderate essential hypertension. The drug sharply increases circulating ANF levels without significantly altering the plasma lipids. In contrast, by increasing the apolipoprotein B content of the LDL fraction, the beneficial cardiovascular effect of a lowered blood pressure may be partly blunted.

Atrial Natriuretic Factor↗
PubMed1990

Colocalization of atrial natriuretic factor (ANF) and estradiol in hypothalamic neurons by combined autoradiography-immunohistochemistry.

The distribution of estrogen target neurons which contain atrial natriuretic factor (ANF) in female rat hypothalamus was investigated by thaw-mount auto-radiography combined with immunocytochemistry using tritium-labeled estradiol and antibodies against ANF. Colocalization of the two hormones was found in the arcuate nucleus, periventricular nucleus, lateral ventromedial nucleus, ventral premammillar nucleus and lateral basal hypothalamus. The percentage of ANF containing cells which concentrate estradiol varies among the different hypothalamic nuclei with the highest number of ANF-positive cells showing nuclear concentration of 3H-estradiol (80-90%) in the nucleus premammillaris ventralis, but less (5-15%) in the other nuclei. These data, together with topographical correspondence in extrahypothalamic brain regions between sites of action of estradiol and production of ANF, suggest extensive interrelationships and modulatory effects of estradiol on ANF production and secretion in the brain, similar to the atrium of the heart.

Animals↗
PubMed1990

Atrial natriuretic factor and cyclic guanosine monophosphate: ion transport in rat colon in vitro and in vivo.

The role of atrial natriuretic factor receptors in the colon is uncertain. Accordingly, the effects of atrial natriuretic factor in vivo and in vitro were studied. In vivo perfusion of the colon in Sprague-Dawley rats was used to measure Na+, K+, Cl-, and water transport, while atrial natriuretic factor was infused into the jugular vein at 0.5 or 1.0 micrograms.kg-1.min-1. In vitro experiments in Ussing chambers measured short-circuit current and ion fluxes before and after atrial natriuretic factor administration. Because cyclic guanosine monophosphate is thought to be a second messenger for atrial natriuretic factor, short-circuit current was also determined before and after exposure to 8-Br-cyclic guanosine monophosphate. Plasma atrial natriuretic factor (atriopeptin III) levels were determined by radioimmunoassay. The in vivo transport of water, sodium, and chloride and the secretion of potassium were not altered by atrial natriuretic factor infusion. In vitro studies showed no change in Na+ or Cl- transport or change in short-circuit current. Plasma atrial natriuretic factor concentrations increased from 139 +/- 55 pg/mL to 1385 +/- 396 pg/mL during infusion, and urine output increased from 12.6 +/- 0.5 microL/min to 37.4 +/- 2.9 microL/min (P less than 0.05). In contrast, 8-Br-cyclic guanosine monophosphate in vitro caused a significant (P = 0.0004) increase in short-circuit current from 1.2 +/- 0.2 to 2.9 +/- 0.3 microEq.cm-2.h-1.

Animals↗
PubMed1990

Immunoreactive atrial natriuretic factor in aqueous humor: its concentration is increased with high intraocular pressure in rabbit eyes.

Atrial natriuretic factor (ANF) concentration in the aqueous humor (AH) was studied in rabbits with experimental glaucoma induced by injecting alpha-chymotrypsin into the posterior chamber. In normal rabbit eyes, the ANF concentration in AH was 3.1 +/- 1.2 pg/ml (mean +/- SEM; n = 12), ranging from 0 to 5.8 pg/ml, whereas it was significantly higher in AH from glaucomatous rabbit eyes, being 81.0 +/- 9.8 pg/ml (n = 12). These findings were correlated with intraocular pressure (IOP), which was 13.0 +/- 2.4 mmHg (n = 12) in normal rabbit eyes and significantly greater in glaucomatous eyes: 24.4 +/- 3.0 mmHg (n = 12). Our data indicate that enhanced ANF release in AH during experimental glaucoma may play an important physiological role in modulating IOP.

Animals↗
PubMed1990

Effects of amlodipine, a long-acting dihydropyridine calcium antagonist in aging hypertension: pharmacodynamics in relation to disposition.

Pharmacodynamics and disposition of amlodipine, a dihydropyridine calcium antagonist, were compared between elderly and young patients with hypertension. Elderly (mean +/- SD; age, 68 +/- 3 years) and young (35 +/- 5 years) patients received single intravenous amlodipine doses followed by oral administration once daily for a total of 12 weeks. After intravenous administration, elderly patients had prolonged elimination half-life values (58 +/- 11 versus 42 +/- 8 hours; p less than 0.01) caused by decreased clearance (19 +/- 5 versus 25 +/- 7 L/hr; p less than 0.01). After a 3-months oral treatment washout period, half-life tended to be prolonged in the elderly patients (69 +/- 20 hours for the elderly patients versus 53 +/- 14 hours for the young patients; difference not significant) and was not markedly different from the short-term intravenous measurement. Both systolic and diastolic blood pressure were significantly decreased from baseline throughout the treatment period, with greater decreases in elderly patients for both systolic and diastolic pressure. When amlodipine plasma concentration was correlated to change in mean blood pressure after short-term intravenous doses, elderly patients had a greater decrease than young patients at a given drug concentration. However, after long-term oral administration, elderly and young patients had comparable decreases in mean blood pressure at a given drug concentration, and the increased antihypertensive effect in the elderly was associated with somewhat higher amlodipine plasma concentration. Amlodipine administered once daily is an effective antihypertensive agent in elderly patients and young patients with essential hypertension.

Administration, Oral↗
PubMed1990

Atrial natriuretic factor in the acute nephritic and nephrotic syndromes.

Because the role of systemic hormones in the pathophysiology of edema in acute renal disease remains incompletely understood, we compared the levels of atrial natriuretic factor (ANF) and plasma renin activity (PRA) in patients with acute glomerulonephritis (AGN), nephrotic syndrome (NS), and normal individuals during salt deprivation and salt loading. Sixteen patients with AGN (10 males) and nine patients with NS and hypoalbuminemia (7 males) were studied on admission, and after recovery (12 AGN patients) or remission (4 NS patients). Eighteen normal controls were each studied after five days on a low (20 mEq Na/day), regular (120 mEq Na/day) and high (300 mEq Na/day) dietary salt intake. Patients with AGN and NS had comparable edema (AGN 2.8 +/- 0.53 kg; NS 3.36 +/- 0.47 kg; SE) and urinary Na excretion (mean +/- SEM: AGN 0.97 +/- 0.11 mEq/hr; NS 1.06 +/- 0.16 mEq/hr), but AGN patients had five times higher ANF (AGN 27.2 +/- 4.06 fmol/ml; NS 5.51 +/- 1.02 fmol/ml; P less than 0.001) and six times lower PRA ng/liter.sec levels (AGN 0.187 +/- 0.047; NS 1.144 +/- 0.222; P less than 0.001) than NS patients. The degree of edema was correlated with ANF levels in AGN patients (P less than 0.001) but not in NS patients. There was a strong exponential negative correlation (r = -0.773, P less than 0.0001) between ANF and PRA, in which AGN patients and Na-restricted controls were located in the opposite ends of the volume sensing-response, and NS patients in the middle, alongside controls with regular Na intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

Correlation of plasma norepinephrine and plasma atrial natriuretic factor during lower body negative pressure.

Plasma atrial natriuretic factor (ANF) is released in proportion to intra-atrial pressures. Plasma norepinephrine (NE) levels are considered to be an indirect reflection of sympathetic tone. These two mediators were studied during human regulation of intravascular volume in the course of exposure to fluid shifts associated with a model of gravitational stress, lower body negative pressure (LBNP.) Blood was drawn from 10 normal subjects before and after exposure to 2 min of a graduated increase in LBNP to a level of 55 mmHg followed by 5 min at 55 mmHg. Plasma ANF was measured by RIA and catecholamines by HPLC-ECD. NE increased from 358 +/- 44 (S.E.M) pg/ml to 511 +/- 48 pg/ml (p = 0.03.) Although ANF only decreased from 27.3 +/- 2.4 pg/ml to 23.5 +/- 2.9 pg/ml (p = 0.33,) a statistically significant negative correlation was observed (r = -0.70, p = 0.02) between the changes in NE and ANF induced by LBNP. The modelling of physiologic responses to gravitational stress in this experiment revealed a negative correlation between changes in sympathetic tone (as reflected by plasma NE) and ANF levels.

Adult↗
PubMed1990

Blockade of volume expansion-induced release of atrial natriuretic peptide by median eminence lesions in the rat.

Since stimulation of the anteroventral third ventricle region (AV3V) induced a rapid elevation of plasma atrial natriuretic peptide (ANP) associated with rapid changes in brain and pituitary content of ANP, whereas lesions of the AV3V were followed by a marked decline in plasma, brain and pituitary content of the peptide, we hypothesized that release of ANP from the median eminence (ME) might be an important pathway to control plasma ANP. Consequently, electrolytic lesions were placed in the ME and the response to hypertonic-volume expansion was determined in conscious rats. In sham-operated controls volume expansion produced a 3.5-fold increase in plasma ANP concentrations within 5 min. Values rapidly declined to near initial levels at 15 and 30 min. Median eminence lesions almost completely blocked the response to volume expansion at 24 and 120 h post-lesion and initial ANP concentrations were lower than those of the sham-operated controls. The results indicate that increased release of ANP from the neurohypophysis may play an important role in the increased plasma ANP concentrations which follow volume expansion.

Animals↗
PubMed1989

Adenosine regulates the release of adrenocorticotropic hormone (ACTH) from cultured anterior pituitary cells.

We have recently shown the presence of adenosine receptors coupled to adenylate cyclase in anterior pituitary and in the present studies we have investigated the effects of adenosine on ACTH release. The 'R'-site specific analogs of adenosine such as N-Ethylcarboxamide adenosine (NECA), L-N6-phenylisopropyl adenosine (PIA), 2-chloro-adenosine (2-Cl-Ado) all stimulated ACTH release in a dose-dependent manner. NECA was the most potent analog and stimulated ACTH release by about 170% with an apparent Ka of 0.1 microM, whereas PIA and 2-Cl-Ado were less potent and stimulated the release by about 110% and 125% with an apparent Ka of 0.2 and 0.4 microM respectively. The stimulation of ACTH release by NECA was inhibited by 3-isobutyl-1-methylxanthine (IBMX). On the other hand, adenosine deaminase (ADA) treatment of the cells also stimulated ACTH release as well as adenylate cyclase activity by about 2-fold, suggesting that endogenous adenosine plays an inhibitory role in the release of ACTH. Other agents, such as corticotropin-releasing factor (CRF), vasoactive intestinal peptide (VIP) and forskolin (FSK) also stimulated ACTH release from these cells. In addition, the stimulation by an optimal concentration of NECA was almost additive with maximal stimulation caused by VIP and FSK. These data suggest that adenosine modulates ACTH release from anterior pituitary through its interaction with adenosine receptors coupled to adenylate cyclase.

Adenosine↗
PubMed1989

Effects of physical exercise and anti-G suit inflation on atrial natriuretic factor plasma level.

The purpose of this study was to measure the effect of enhanced venous return on atrial natriuretic factor (ANF) secretion during exercise and upright posture and the consequences on renin angiotensin aldosterone system (RAAS) activity. Six healthy male subjects were submitted to four different procedures. All procedures were performed in the same position, i.e. riding on a support with legs hanging. Two procedures were performed at rest: the subjects were studied after a 25-min rest in this position, with and without the lower limb fitted with an anti-G suit inflated to 60 mmHg. Two procedures were carried out with physical exercise; arm-cranking was performed in the same position with and without the anti-G suit inflated to 60 mmHg. Venous blood was collected before and after each procedure in order to measure plasma ANF, plasma aldosterone concentration (PAC), plasma renin activity (PRA), corticotrophin (ACTH) and catecholamine level. The data mean +/- SEM showed that the ANF plasma level decreased significantly (p less than 0.05) from 32.5 +/- 4 to 28 +/- 6 pg.ml-1 after a 20-min rest in the upright posture, whereas this effect was absolished with anti-G suit inflation. Physical exercise with and without the anti-G suit increased the ANF level above control values (60 +/- 13.6 pg.ml-1 and 53 +/- 13 pg.ml-1): anti-G suit inflation had no significant effect. PRA increased after rest in an upright posture and during physical exercise; anti-G suit inflation abolished this increase in both conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Identification and characterization of atrial natriuretic factor receptors in the rat retina.

The characteristics of atrial natriuretic factor (ANF) receptors where studied in rat retinal particulate preparations. Specific 125I-ANF binding to retinal particulate preparations was greater than 90% of total binding and saturable at a density (Bmax) of 40 +/- 8 fmol/mg protein with an apparent dissociation constant (Kd) of 6.0 +/- 2.0 pM (n = 3). Apparent equilibrium conditions were established within 30 min. The Kd value of 125I-ANF binding calculated by kinetic analysis was 4.0 pM. The Bmax of 60 +/- 10 fmol/mg protein and the Kd of 5 +/- 2 pM, calculated by competition analysis, were in close agreement with the values obtained from Scatchard plots or kinetic analysis. The 125I-ANF binding to retinal particulate preparations was not inhibited by 1 microM concentration of somatostatin, vasopressin, vasoactive intestinal peptide, adrenocorticotropin, thyrotropin releasing hormone, or leu-enkephalin. The rank order of potency of the unlabelled atrial natriuretic peptides for competing with specific 125I-ANF (101-126) binding sites was rANF (92-126) greater than rANF (101-126) greater than rANF (99-126) greater than rANF (103-126) greater than Tyro-Atriopeptin I greater than hANF (105-126) greater than rANF (1-126). Similar results have been obtained in peripheral tissues and mammalian brain, indicating that central and peripheral ANF-binding sites have somewhat similar structural requirements. Affinity cross-linking of 125I-ANF to retinal particulate preparations resulted in the labelling of two sites of molecular weight 140 and 66 kDa, respectively. This demonstration of specific high-affinity ANF receptors suggests that the peptide may act as a neurotransmitter or neuromodulator in the retina.

Affinity Labels↗
PubMed1989

Role of the hypothalamus in the control of atrial natriuretic peptide release.

Stimulation of the region antero-ventral to the third cerebral ventricle (AV3V) by a cholinergic drug, carbachol, and lesions of the AV3V have been demonstrated in previous studies to either augment or decrease sodium excretion, respectively. Atrial natriuretic peptide (ANP) dramatically increases renal sodium excretion and has been localized to brain areas previously shown to be involved in control of sodium excretion. Consequently, to evaluate a possible role of brain ANP in evoking the changes in renal sodium excretion that follow stimulations or lesions of the AV3V, we determined the effect of injection of carbachol into the AV3V of rats on the concentration of plasma ANP and its content in several neural tissues, the pituitary gland, lungs, and atria. Conversely, the effect of lesions in the AV3V on plasma ANP and the content of the polypeptide in the various organs was determined. Injection of carbachol into the AV3V produced the expected natriuresis, which was accompanied within 20 min by a dramatic rise in the plasma ANP concentration and a rise in ANP content in the medial basal hypothalamus, the neurohypophysis, and particularly the anterior hypophysis but without alterations in the content of ANP in the lungs or the right or left atrium. Conversely, there was a dramatic decline in plasma ANP at both 24 and 120 hr after the AV3V lesions had been placed. This was accompanied by a slight decline in the content of the peptide in the lungs. There was no change in its content in the right atrium at 24 hr after lesions, but there was a significant increase at 120 hr. There was a small decline in the content in the left atrium at 24 hr, followed by a rebound to slightly elevated levels at 120 hr. These small changes contrasted sharply with the dramatic decline in content of the peptide in the medial basal hypothalamus, median eminence, neurohypophysis, choroid plexus, anterior hypophysis, and olfactory bulb. These declines persisted or became greater at 120 hr; except in the olfactory bulb in which the decline was no longer significant. The dramatic increase in plasma ANP after carbachol stimulation of the AV3V that was accompanied by marked elevations in content of the peptide in basal hypothalamus and neuro- and adenohypophysis suggests that the natriuresis resulting from this stimulation is brought about at least in part by release of ANP from the brain. Conversely, the dramatic decline in plasma ANP after AV3V lesions was accompanied by very dramatic declines in content of ANP in these same structures, which suggests that the previously shown decrease in sodium excretion obtained after these lesions may be at least in part due to a decrease in release of ANP from the brain. In view of the much larger quantities of the peptide stored in the atria, it is still possible that changes in atrial release may contribute to the alterations in plasma ANP observed after stimulation or ablation of the AV3V region; however, these results suggest that the dramatic changes in plasma ANP that followed these manipulations may be due to altered release of the peptide from brain structures as well as the atria and lungs.

Animals↗
PubMed1989

Effect of prolonged infusion of ANF in normotensive and hypertensive monkeys.

It is now recognized that bolus and short-term infusions of atrial natriuretic factor (ANF) into different species lead to a slight and transient decrease of blood pressure, while prolonged infusions cause a significant blood pressure reduction in hypertensive but not in normotensive rats. The present study was designed to evaluate the effects of prolonged ANF infusions on blood pressure and humoral parameters in normotensive and hypertensive African green monkeys (Cercopithecus aethiops). Human-ANF infusions (100 ng/kg.hr) in conscious, normotensive vervets for a period of 48 hours evoked highly significant decreases of blood pressure (from 124/65 to 104/53 mm Hg), plasma renin activity, aldosterone, and hematocrit. This fall in blood pressure was not accompanied by an increase of plasma cGMP levels at the end of the infusion. Forty-eight hours after the infusion was terminated, the decrease in blood pressure was still significant (97/46 mm Hg), as was the drop in aldosterone. In hypertensive monkeys, systolic blood pressure declined from 175 +/- 8 to 130 +/- 8 mm Hg, while diastolic pressure fell from 117 +/- 10 to 88 +/- 4 mm Hg. These data demonstrate that the chronic infusion of ANF in both normotensive and hypertensive vervets has more profound effects than does acute bolus administration, effects that persist for a prolonged period of time after discontinuation of the infusion.

Animals↗
PubMed1989

Does the olfactory system mediate water- and mineral-regulating mechanisms? Evidence of immunoreactive atrial natriuretic factor within olfactory mucosa.

The immunoreactivity of atrial natriuretic factor (ANF) was studied in the rat olfactory mucosa (OM). Endogenous immunoreactive ANF (IR-ANF) was purified from OM using Vycor glass beads for extraction and reverse-phase HPLC: two of three IR-ANF peaks, identified by retention time, were identical to both the circulating form of ANF (Ser99-Tyr126) and the ANF pro-hormone (Asn1-Tyr126). A radioreceptor assay, employing rat renal glomerular membranes, revealed that endogenous IR-ANF competed with radiolabelled ANF. IR-ANF was localized by immunocytochemistry in secretory cells of Bowman's gland and in some cells of the epithelial layer. The relatively low concentration of IR-ANF in the OM (2.5 ng/mg protein) suggests a local role of ANF in this tissue. This hypothesis is supported by the presence in OM of ANF-binding sites, characterized by a KD of 95 pM and a Bmax of 130 fmol/mg protein. We propose that ANF could be released from the OM and act throughout in a paracrine (if not autocrine) manner on some yet-unidentified targets containing ANF-binding sites.

Animals↗
PubMed1989

Lung is an important source of atrial natriuretic factor in experimental cardiomyopathy.

The regulation of water and electrolyte homeostasis is multifactorial and includes the heart and kidneys as important regulatory centers. Within the heart, a recently discovered hormone, atrial natriuretic factor (ANF), has been implicated in the maintenance of water and salt balance. Primarily found in mammalian atria, ANF has been detected in low amounts in several tissues, including lungs. A disorder of the ANF system has been demonstrated in genetically cardiomyopathic hamsters, a model for human congestive cardiomyopathy. Atrial ANF gene expression and storage are decreased during development of this disease, while paradoxically, circulating levels of ANF are increased. We have hypothesized that an extracardiac source may contribute to ANF production in these pathological conditions. In this paper we provide evidence that ANF synthesis is stimulated in the lungs of hamsters during development of cardiomyopathy as revealed by increased ANF mRNA and peptide levels. Furthermore, we show that ANF synthesized in lungs is secreted and has identical chromatographic and biological properties to circulating ANF. The increased production of ANF in lungs may be physiologically important in preventing pulmonary edema. Alternatively, during cardiac dysfunction, lungs may play a compensatory role by increasing their contribution to plasma ANF levels.

Animals↗
PubMed1989

Effect of brain natriuretic peptide on dehydration- or angiotensin II-induced water intake in rats.

The present study was performed to evaluate the effect of 3rdV injection on water intake of brain natriuretic peptide (BNP), which is structurally different from the atrial natriuretic peptide. BNP was recently isolated from porcine brain and appears to have a different precursor than the family of atrial natriuretic peptides. Central administration of BNP 3rdV decreased water intake. At a dose of 2.0 nmol/rat, BNP partially inhibited dehydration-induced water intake and completely blocked the stimulatory effect of 478 pmol/rat angiotensin II in rats.

Angiotensin II↗