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Biomedical subjects

R Gerzer

Publications and source records attributed to R Gerzer.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of a cloned ANF-sensitive guanylate cyclase (GC-A) with particulate guanylate cyclase from adrenal cortex.

Recently, an ANF-sensitive guanylate cyclase (GC-A) has been cloned from a rat brain cDNA library. Here we studied the stimulation of cyclic GMP accumulation in response to atrial natriuretic factor (ANF), urodilatin and atriopeptin I (AP-1) in a rat glioma C6 cell line permanently transfected with GC-A as well as GC-A activity in membranes from these C6 cells and in membranes from COS-7 cells that were transiently transfected with GC-A. We also measured binding affinities for these natriuretic peptides in the membrane preparations. These characteristics of GC-A were compared to those of membrane preparations from adrenal cortex of bovine and human origin. The order of potency of stimulation of cyclic GMP accumulation in permanently transfected glioma cells was ANF greater than urodilatin greater than AP I; AP I stimulated cyclic GMP accumulation. A similar order of potency was obtained for stimulation of guanylate cyclase activity in membranes from permanently transfected glioma cells as well as from transiently transfected COS-7 cells. In contrast, AP-1 was uneffective to stimulate guanylate cyclase in membrane preparations from adrenal cortex from bovine as well as from human origin. Furthermore, urodilatin was equipotent to ANF in these preparations. Binding affinities were comparable for ANF and urodilatin in membranes from cells transfected with GC-A and in membranes from adrenal cortex of both sources, whereas AP-1 had a weaker affinity in all preparations studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1992

Effects of atrial natriuretic factor on anterior pituitary hormone secretion in normal man.

The effects of intravenous human atrial natriuretic factor ANF(99-126) administration on anterior pituitary hormone secretion have not been extensively investigated in humans. We repeatedly studied 10 healthy volunteers (5 female, 5 male, aged 28 +/- 2 years) on 2 occasions, 3 days apart. In randomized, single blind order, subjects received pretreatment with either placebo or intravenous ANF(99-126) (bolus 100 micrograms/kg, 30-min infusion of 0.1 micrograms/kg.min). Subsequently on both occasions subjects received a combined intravenous bolus injection of pituitary releasing hormones (200 micrograms thyrotropin releasing hormone, 100 micrograms gonadotropin releasing hormone and 100 micrograms human adrenocorticotropin releasing hormone; Bissendorf, Hannover, FRG). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), thyrotropin (TSH), prolactin, ANF and cyclic guanosine monophosphate (GMP) were determined by radioimmunoassay. ANF(99-126) treatment induced a significant reduction in basal ACTH plasma concentrations and tended to decrease basal plasma cortisol. The TSH response to combined releasing hormone administration was significantly diminished after ANF(99-126) pretreatment. In women, the releasing hormone induced prolactin increase was reduced after ANF(99-126) pretreatment. With the present study design, ANF(99-126) did not alter the basal or releasing hormone stimulated plasma concentrations of cortisol, LH, FSH and GH. Releasing hormone administration did not affect ANF and cyclic GMP plasma levels. In humans, effects of natriuretic peptides on anterior pituitary hormone secretion may have to be considered with investigational or therapeutic administration of ANF analogues or agents interfering with the ANF metabolism.

Adult↗
PubMed1992

Effects of graded exercise on blood pressure, heart rate, and plasma hormones in cardiac transplant recipients before and during antihypertensive therapy.

The effects of graded supine ergometry on blood pressure, heart rate, and plasma hormones were studied in 14 hypertensive heart transplant recipients before and after 2 weeks and 6 months of enalapril (20 mg/day) plus furosemide (20-80 mg/day) alone or combined with verapamil (120-360 mg/day). Each time, measurements were obtained at rest and at 25 and 50 W exercise. Antihypertensive therapy normalized blood pressure, while heart rate and the blood pressure response to exercise remained unaltered. Pretreatment resting plasma renin activity and catecholamine levels were normal, while atrial natriuretic factor and cyclic guanosine monophosphate concentrations were elevated. All hormones increased significantly with exercise. During treatment, plasma renin activity increased and atrial natriuretic factor and cyclic guanosine monophosphate levels decreased significantly, with a blunted exercise response; concentration of catecholamines increased significantly, with augmented exercise response. Thus, the chosen regimen allowed effective, lasting BP control in hypertensive transplant patients but was associated with significant changes in plasma hormones. Whereas the rise in plasma renin activity may be attributed to converting enzyme inhibition, the decreases in atrial natriuretic factor and cyclic guanosine monophosphate and increases in catecholamine levels seem to indicate marked changes in resting and particularly exercise hemodynamics during antihypertensive therapy.

Adult↗
PubMed1992

Haemodynamic and renal effects of urodilatin bolus injections in patients with congestive heart failure.

Urodilatin (ANF(95-126)) is an analogue of the atrial natriuretic factor (ANF(99-126)), which has been isolated from human urine. Recently we have shown in healthy volunteers, that intravenous bolus injections of synthetic urodilatin produce more pronounced reductions of pulmonary arterial pressure than ANF(99-126). To compare haemodynamic and renal effects of synthetic urodilatin with those of ANF(99-126) in congestive heart failure (CHF), 12 patients (66.3 +/- 1.4 years) received either two high dose intravenous bolus injections of 4 micrograms kg-1 bw Urodilatin (URO) at a 30 min interval (n = 6) or the same doses of ANF(99-126) (n = 6). Prior to i.v. URO, no URO immunoreactivity was found in human plasma (specific RIA, no crossreactivity to ANF). Similar to ANF, the increase in diuresis (1.4 +/- 0.7 to 3.7 +/- 1.6 ml min-1) and natriuresis (169 +/- 114 to 430 +/- 197 mumol min-1) was moderate after URO in CHF. During the 90 min study period, mean plasma cyclic GMP levels increased much more after URO (by 53.4 +/- 15.1 nM) than after ANF (by 13.1 +/- 3.0 nM; P = 0.04). In contrast to ANF, i.v. bolus injections of URO produced sustained haemodynamic effects in CHF lasting up to 90 min: The average (0-90 min) reduction of systemic vascular resistance was more pronounced after URO (-578 +/- 148) than after ANF (-204 +/- 65 dyn*s*cm-5, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Haemodynamic and renal effects of urodilatin in healthy volunteers.

Urodilatin (ANF(95-126)), an analogue of the atrial natriuretic factor (ANF(99-126)), has recently been isolated from human urine. To study haemodynamic and renal effects of synthetic urodilatin, 18 healthy male volunteers (age 26.1 +/- 0.8 years; X +/- SEM) received i.v. bolus injections of urodilatin at doses of 1, 2 or 4 micrograms kg-1 body weight (bw) (n = 6 per dosage group). Urodilatin dose-dependently increased heart rate and cardiac index. A dose-dependent increase in plasma cyclic GMP levels was also observed. Urinary cyclic GMP excretion, urine flow and natriuresis increased 7-fold, 5-fold and 4-fold, respectively. Renal effects were not different between dosage groups. Compared with ANF(99-126), after urodilatin the reduction in mean pulmonary arterial pressure (PAP) was more pronounced (2 micrograms kg-1, n = 6; ANF -1.8 +/- 0.5, URO: -5.5 +/- 1.1 mmHg, P less than 0.05). Furthermore, after urodilatin the reduction of PAP lasted continuously from 2 up to 90 min after injection, while ANF(99-126) produced only a transient decrease of PAP. Similarly the reduction of pulmonary capillary wedge pressure (PCWP) by urodilatin from 9.3 +/- 1.2 to 3.8 +/- 0.9 mmHg (P less than 0.05) was also sustained up to 90 min post administration. These data in healthy volunteers suggest that, due to prolonged reduction of PAP and PCWP with increases of cardiac index and reduction of systemic vascular resistance, urodilatin might exhibit beneficial effects in cardiovascular disease.

Adult↗
PubMed1992

Roles of cephalic Na+ concentration and urodilatin in control of renal Na+ excretion.

Effects on renal function of an increase in the concentration of sodium in the blood supplying the head were investigated in water-diuretic conscious dogs in which the sodium and water contents were controlled by separate servo-mechanisms. A selective 2% increase in the sodium concentration of the carotid blood was achieved by a split-infusion technique including infusions of hypertonic saline into both carotid arteries and water into a jugular vein at rates making the combined infusate isotonic. This procedure caused a 34-fold increase in renal sodium excretion concomitant with a fourfold increase in the rate of urinary excretion of urodilatin. A comparable isotonic volume expansion (isotonic saline infusion into carotid arteries and jugular vein) caused a significantly smaller (13-fold) increase in urinary rate of excretion of sodium (P less than 0.02) and no increase at all in the excretion of urodilatin. It is hypothesized that cephalic sodium concentration receptors regulate the rate of excretion of sodium via urodilatin even under the present slightly hypotonic conditions.

Animals↗
PubMed1992

Effects of an acute saline infusion on fluid and electrolyte metabolism in humans.

Several hormonal systems participating in body fluid and electrolyte homeostasis were investigated in six healthy volunteers in a supine body position during a period of 9 days and nights. Under strictly controlled conditions, striking circadian rhythms were observed for plasma levels of vasopressin, renin, aldosterone, guanosine 3',5'-cyclic monophosphate, cortisol, and epinephrine. Nocturnal decreases and diurnal increases in urine flow rate and urinary excretion of electrolytes were observed and closely paralleled the urinary excretion of urodilatin. During 48 h after an acute isotonic saline infusion (2 liters within 25 min) and after a 48-h control experiment the urinary excretion of H2O and electrolytes, and simultaneously the alterations in endocrine systems participating in body fluid homeostasis, were determined. Urine flow and urinary electrolyte excretion rates were significantly increased during 2 days after the saline infusion. The largest increase in urinary fluid and electrolyte excretion was observed between 3 and 22 h postinfusion. These long-term changes were paralleled by altered H2O and Na balances and also by elevated body weights that returned to baseline values with an approximate half-life of 7 h. These data suggest that vasopressin, atrial natriuretic peptide, and catecholamines are unlikely to be of major importance for the renal response to this hypervolemic stimulus. The renin-aldosterone system was suppressed during 2 days postinfusion. This suppression correlated with the effects of saline load on Na excretion. However, the closest relation with Na excretion was observed for the kidney-derived member of the atrial natriuretic peptide family, urodilatin, which was considerably increased during the long-term period up to 22 h postinfusion. Thus these data show that the human body in supine position requires approximately 2 days to regulate the amount of Na and H2O provided by an acute saline infusion. The data also suggest that urodilatin and the renin-aldosterone system might participate in the long-term renal response to an acute saline infusion and also in the mediation of circadian urinary excretion rhythms.

Adult↗
PubMed1992

The postdialytic plasma cyclic guanosine 3':5'-monophosphate level as a measure of fluid overload in chronic hemodialysis.

The postdialytic plasma level of cGMP, a marker for the release of atrial natriuretic peptide (ANP) in humans, is closely related to hypervolemia in chronic hemodialysis patients. In order to test the practicability of routine postdialysis cGMP determination for the detection of fluid overload, ANP and cGMP levels in the total hemodialysis population of 81 patients were measured with blood samples drawn immediately after hemodialysis. Twenty-three patients had a cGMP level of more than 20 pmol/mL. In 13 of these, pulmonary congestion was present on the chest roentgenogram. Two of these patients refused a gradual reduction of their dry body weight. In the remaining 21 patients, the weight reduction was associated with a decrease in cGMP levels in all cases and with a decrease in ANP levels in all but two cases. Fourteen of the 21 patients reached a cGMP level below 20 pmol/mL after weight reduction, and at that time, none of these showed signs of pulmonary congestion on chest x-ray. All seven patients, whose cGMP levels remained above 20 pmol/mL despite the reduction, had documented heart disease with impairment of left ventricular function. These results suggest that the plasma cGMP level after hemodialysis is more apt for the determination of dry body weight than is ANP or a chest roentgenogram.

Adult↗
PubMed1992

Diuresis and natriuresis following isotonic saline infusion in healthy young volunteers before, during, and after HDT.

In the present study the response to acute saline loading was investigated. During a 24-day study period six male subjects followed a standardized diet including a daily intake of 40 ml water and 125 mg NaCl per kg body weight. Before, during, and after a ten-day period of 6 degrees head down tilt (HDT) each volunteer received an intravenous 0.9% saline infusion of 22 ml/kg body weight over 20 minutes. HDT produced significant losses in body weight and in blood volume, but the responses to saline loading were similar during all phases of the study. Plasma levels of atrial natriuretic peptide (ANP) did not increase, while plasma levels of cyclic GMP increased by about 40% 90 minutes after each infusion. Urine flow nearly doubled during second hour post-infusion. Sodium excretion showed a 3-fold increase and remained elevated during the third hour, while potassium excretion was significantly reduced. Urinary excretion of cyclic GMP reached a peak during the second hour post-infusion. At the end of these short-term periods the cumulative water- and sodium-balance data disclosed that only about 20% of the infused water and less than 15% of the infused sodium was excreted during each experiment. In addition to the short-term renal response, urine flow and sodium excretion remained significantly elevated for more than 48 hours after each saline load. The long-term renal response was paralleled by an increased excretion of urinary cyclic GMP. HDT produced significant changes in body fluid distribution, but only minor changes in the regulatory responses to an acute saline load. We conclude from these data that the excretion of an acute isotonic saline load requires several days and that the renal response appears to be independent of the secretion of ANP from the heart.

Adult↗
PubMed1992

Effects of head-down tilt and saline loading on body weight, fluid, and electrolyte homeostasis in man.

We studied the effects of head-down tilt bedrest (HDT) on body weight, fluid and sodium homeostasis. A fluid load session with rapid intravenous infusion of 22 ml/kg body weight (BW) isotonic saline was performed before, during and after HDT. During the pre- and post HDT periods the test subjects were given a diet containing 2600 kcal/day. The energy intake was reduced to 2000 kcal/day during HDT. Water intake was kept constant at 40 ml/kg BW, sodium intake was 2.2 mmol/kg BW and protein intake was 1.4 g/kg BW, while the daily fat and carbohydrate intake was reduced during the HDT period. As expected plasma volume and BW changed rapidly in the beginning of HDT and during early recovery. A total body water loss of 0.6 l was observed within the second day after tilting. Plasma volume was reduced by 16% during HDT-bedrest. The time course of the body fluid loss paralleled a decrease in body sodium that then remained fairly constant during the HDT-bedrest period (except for the interference caused by the fluid loading on day S06). A restoration of body fluid and body sodium content occurred early in the recovery period. Fluid loading caused a negative fluid balance of 0.6-0.9 l over a 48 hr period following infusion regardless of the phase of the HDT study. These results demonstrate that under our strictly controlled conditions 1) HDT alters body fluid and sodium balances, 2) a standard fluid loading causes a net negative 3-day fluid balance during all phases of the study.

Adult↗
PubMed1991

Isolation and expression of a guanylate cyclase-coupled heat stable enterotoxin receptor cDNA from a human colonic cell line.

Heat stable enterotoxins (STs) are low molecular-weight peptides secreted by enterotoxigenic bacteria. One type of these enterotoxins (STa) induces intestinal secretion leading to acute diarrhea by binding to a membrane form of guanylate cyclase. We have isolated a cDNA from a human colonic cell line, T84, encoding for a guanylate cyclase-coupled enterotoxin receptor (STaR). The predicted amino acid sequence of the human STa receptor is 81% identical with the previously cloned enterotoxin receptor (GC-C) from rat intestine. COS-7 cells transiently transfected with the cloned cDNA expressed specific concentration-dependent response to STa as measured by cyclic GMP accumulation and is about 20 times more sensitive to the stimulation by STa than has been shown for GC-C.

Amino Acid Sequence↗
PubMed1991

Functional modulation of ANF-sensitive particulate guanylate cyclase by redox mechanisms.

We examined the effects of sulfhydryl-reactive redox agents and of the apparent oxidation-reduction (redox) potential of the assay medium on enzyme activity and atrial natriuretic factor (ANF) binding properties of particular guanylate cyclase from bovine adrenal cortex. Redox potential was varied by addition of redox-reactive agents and quantified by electrochemical measurement. The modification of free SH groups by thiol-reactive agents had only a minor effect on ANF binding or on the extent of ANF-dependent enzyme stimulation whereas free thiol groups were essential for basal enzyme activity of ANF-sensitive particulate guanylate cyclase. Basal and ANF-stimulated particulate guanylate cyclase activity was modulated by exposure to different redox potential states. This modulation was different for the substrates Mg.GTP and Mn.GTP. The apparent redox potential had no influence on the extent of guanylate cyclase activation by ANF. Our results suggest that critical free thiol groups, which are sensitive to thiol-reactive redox agents, are involved in the catalytic, but not in the receptor function of ANF-sensitive particulate guanylate cyclase. These thiol groups could be the structural basis for the effects of redox events which modulate basal enzyme activity, but not activation by ANF.

Adrenal Cortex↗
PubMed1991

Autoradiographic localization of [125I]-C-ANP compared to [125I]-ANP in rat tissue.

Whole-body autoradiography demonstrated the different distribution of [125I]-C-ANP and [125I]-ANP to rat tissues. Highest enrichment of radioactivity of both labelled peptides was found in the kidney. In some organs we found remarkable differences between [125I]-ANP and [125I]-C-ANP. In the kidney cortex, especially in the glomeruli, as well as in the endocardium, the zona glomerulosa and the medulla of the adrenal gland, where high levels of radioactivity after [125I]-ANP administration were detected, no or just few radioactivity was found after administration of [125I]-C-ANP. On the other hand in the kidney papilla and the outer subcortical medulla, characteristic blackening was found after [125I]-C-ANP administration. Those differences might be important for the understanding of pharmacological actions of ANP analogues.

Adrenal Glands↗
PubMed1991

Comparison of anti-platelet properties of molsidomine, isosorbide-5-mononitrate and placebo in healthy volunteers.

The purpose of the present work was to investigate the ex vivo platelet-inhibiting properties of the nitric oxide-containing vasodilator, molsidomine, and the organic nitrate, isosorbide-5-mononitrate, in comparison with placebo. Ex vivo platelet aggregation in 11 healthy volunteers was measured before, as well as 30 and 60 min after, the intake of either 4 mg molsidomine, 20 mg isosorbide-5-mononitrate (ISMN) or placebo in a randomized double-blind fashion. The release of thromboxane was also determined. Threshold doses of platelet-activating factor (PAF) to induce irreversible aggregation were significantly increased by 100 and 120% 30 and 60 min after molsidomine. Slopes of aggregation curves (aggregation induced with 50 and 200 nM PAF) were significantly reduced after molsidomine (P less than 0.01). Small platelet-inhibiting effects were also observed after ISMN and after placebo intake. The release of thromboxane was not influenced when platelets were maximally stimulated either during clotting of whole blood or during aggregation of platelet-rich plasma with a high dose of PAF. Thromboxane release with a low dose of PAF was reduced 30 and 60 min after drug intake, independent of whether molsidomine, ISMN or placebo was applied. The data indicate that the usual clinical doses of molsidomine, but not of ISMN inhibit platelet aggregation in healthy man.

Adult↗