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Biomedical subjects

W G Forssmann

Publications and source records attributed to W G Forssmann.

At least 19 recordsLinked to original sources
PubMed1992

Urodilatin: a new peptide with beneficial effects in the postoperative therapy of cardiac transplant recipients.

Renal failure after heart transplantation (HTx) still remains a serious problem, especially when cyclosporin A is used for immunosuppression in the early postoperative therapy. To preserve good renal function without reducing immunosuppressive cyclosporin A treatment, we administered urodilatin (CDD/ANP-95-126) in a long-term, low-dose infusion in addition to the usual medication after heart transplantation. From November 1990 to June 1991, 51 patients (46 male and 5 female; mean age 48 years) were treated with a 6-20 ng/kg bw.min infusion for 96 h after HTx. The renal function and hemodynamic parameters of these urodilatin-treated patients were compared in this sequential study with 40 patients (33 male and 7 female; mean age 49 years) who had undergone HTx previously from May to November, 1990, as controls. In this phase IIa study, both groups did not differ significantly with respect to age, sex, indication for HTx, and preoperative renal function. In comparison with controls patients treated with urodilatin had a significantly better renal function: a reduction in the peak plasma creatinine (PC values day 4: 1.5 +/- 0.11 vs. 2.19 +/- 0.19 mg/dl; P = 0.002), a lower peak serum urea (SU values day 4: 109 +/- 8 vs. 154.7 +/- 8.94 mg/dl; P = 0.0036), and a lower incidence of hemodialysis (6% vs. 10%) were observed. Adequate diuresis was maintained in spite of the reduction of furosemide by more than 60% (P = 0.005) on each day of urodilatin infusion in comparison with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1992

Ultrastructural and immunocytochemical study of the myoendocrine cells of the fish Hypostomus cordovae.

The myoendocrine cells of the heart of Hypostomus cordovae (Günther 1880), a teleost fish from South America, were investigated by electron microscopy and immunohistochemistry. By applying antibodies raised against synthetic cardiodilatin 99-126 (CDD/ANP 99-126), a specific labeling of this hormone was found in the heart of this fish, mainly in myoendocrine cells of atrial trabeculae, where specific secretory granules are stored. The distribution of secretory granules exhibited striking seasonal variations. In winter there were fewer differentiated myoendocrine cells, which were easily recognized by the presence of specific secretory granules, most of which occur clustered in perinuclear areas of the cells. By contrast, in summer the majority of the myocardic cells of the atrium are active endocrine cells. They contain abundant secretory granules widely scattered in the cytoplasm, many of them polarized toward the subendocardial aspect of the cell. The secretory granules can be easily differentiated from the Weibel-Palade granules of endothelial cells, the shape, size and content of which were typical at electron-microscopic level. In addition, these endothelial granules did not display CDD immunoreactivity. The presence of cardiodilatin in a fish such as Hypostomus cordovae further supports the view that cardiac hormones are present in many Vertebrates and may preserve analogous roles such as those reported in other species throughout the group.

Animals↗
PubMed1992

Distribution patterns and coexistence of neurohormonal peptides (ANP, BNP, NPY, SP, CGRP, enkephalins) in chromaffin cells and nerve fibers of the anuran adrenal organ.

Immunohistochemical techniques were used to study the adrenal organs of the anuran species Rana esculenta, Caldula pulchra and Bufo marinus with respect to the distribution and coexistence of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), Leu-enkephalin (Leu-ENK). Met-enkephalin-Arg-Phe (MEAP) and dynorphin A 1-17 (DYN). Antisera against enzymes involved in catecholamine synthesis, i.e., dopamine-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH), were used for the identification of chromaffin cells. ANP-immunoreactive (-IR) cells occurred in high densities (30%-70% of the total cell population) in all species investigated. In C. pulchra and B. marinus, BNP-IR cells constituted a population of non-DBH-IR and non-TH-IR cells that were different from the ANP-IR cells. A large proportion of the adrenal cells (10%-55%) were immunoreactive to Leu-ENK, and a minority (2%-5%) showed MEAP-immunoreactivity. DYN-immunoreactivity was not observed. The anurans studied exhibited small numbers of SP-IR, CGRP-IR and NPY-IR cells. Immunoreactivities for ANP + Leu-ENK and Leu-ENK + MEAP were shown to coexist. In C. pulchra and B. marinus, immunoreactions for ANP + NPY, ANP+SP and SP + CGRP were also colocalized. Except for DYN, all neurohormonal peptides also occurred in intra-adrenal nerve fibers. SP-IR fibers also displayed CGRP-immunoreactivity and some Leu-ENK-IR fibers contained MEAP-immunoreactivity. In C. pulchra, NPY-IR fibers were found that also showed ANP-immunoreactivity.

Adrenal Glands↗
PubMed1992

Relaxation of non-contracted smooth muscle by atrial natriuretic peptide.

Atrial natriuretic peptide (alpha-hANP-99-126), 1 x 10(-8) to 5 x 10(-10) M was able to further relax the non-contracted aortic smooth muscle of rabbit after complete recovery from a previous challenge with human angiotensin II (AII), 1 x 10(-6) M. The relaxation was directly proportional to the response of the ring or strip to the previous challenge with AII. ANP does not have effect on basal tension in isolated strips or rings of the rabbit aorta not previously exposed to AII. Norepinephrine (NE), 10(-7) M was less potent in inducing reactivity of the vessel to ANP, ie, only a small relaxant effect on basal tension could be observed. A similar vasorelaxant effect of ANP on basal tension could be obtained in the absence of extracellular calcium: Ca(2+)-free Ringers' solution containing 2 mM ethylene-glycol-bis (beta-aminoethyl ether)N',N' tetraacetic acid (EGTA-Ringer). In contrast, sodium nitroprusside 10(-8) M does not affect basal tension. Present results demonstrate the role of the physiological state of the vessel in the reactivity to ANP.

Angiotensin II↗
PubMed1991

Atrial natriuretic peptide-like immunoreactive cells in the guinea pig inner ear.

Using specific antibodies against cardiodilatin/atrial natriuretic peptide (CDD/ANP) in a conventional immuno-histochemical method (PAP) we located ANP/CDD-like immuno-reactive cells related to the secretory area, to the sensory and to the neuronal area in the compartments of the inner ear (cochlea, utricle/ampulla, and endolymphatic sac). Immunoreactive cells were unevenly distributed in the different compartments as well as within the cochlear space. Our findings suggest that ANP/CDD may play a role in the local control of fluid and electrolyte homeostasis of the inner ear. ANP/CDD-binding sites and ANP/CDD-like immunoreactivity in the inner ear may also indicate that the peptide has an additional paracrine and/or autocrine function in the organ.

Animals↗
PubMed1991

Intrinsic pancreatic nerves after mechanical denervation of the extrinsic pancreatic nerves in dogs.

Little is known about the influence of cutting the extrinsic pancreatic nerves on the morphology and function of the intrapancreatic nerves in dogs. For this reason, intrapancreatic nerves of mongrel dogs were studied, using electron microscopy and immunohistochemistry, after truncal vagotomy, after celiac and superior mesenteric ganglionectomy, and after a combination of both operations, i.e., removing all extrinsic nerves of the pancreas. Dogs with intact extrinsic and intrinsic pancreatic nerves served as controls. Studies were performed 1-2 weeks and up to 5 months after one or both denervation procedures. For immunohistochemical and electron microscopic studies the animals were perfused with glutaraldehyde-formaldehyde-picric acid solution and the tissue was embedded in Epon or paraffin. Both immunohistochemical and electron microscopic studies revealed that signs of degenerating intrapancreatic nerves occurred only in the early phase (up to 30 days) after operation. After 60 days, hypertrophy of pancreatic nerve fibers was observed. The most striking finding was that the integrity of the intrapancreatic ganglia and nerves was almost preserved after complete extrinsic denervation. In controls there was a strong intrapancreatic innervation with vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI), substance P (SP), and neuropeptide Y (NPY) nerves. SP and NPY-nerves significantly decreased after the different denervation procedures, but the other peptidergic nerves were not altered by truncal vagotomy, ganglionectomy, or the combination of both procedures. We conclude that the dog pancreas contains extensive intrinsic peptidergic nerves, which, with the exception of SP and NPY-nerves, are greatly independent of the integrity of the extrinsic nerves.

Animals↗
PubMed1990

Effects of ANP-(95-126) in dogs before and after induction of heart failure.

In conscious dogs with and without congestive heart failure, we investigated hemodynamic, hormonal, and renal effects of a new natriuretic peptide [ANP-(95-126)]. Unlike ANP-(99-126), which is secreted in the heart and rapidly inactivated in the kidney, ANP-(95-126) most likely originates from the kidney and is not destroyed by proteolysis in membrane preparations of kidney cortex. In healthy animals intravenous ANP-(95-126) significantly decreased mean arterial pressure, cardiac output, stroke volume, and right atrial pressure and increased heart rate without changing mean pulmonary arterial pressure and total peripheral vascular resistance. In dogs with congestive heart failure, ANP-(95-126) showed no effects on mean arterial pressure, cardiac output, stroke volume, and peripheral vascular resistance but reduced right atrial pressure and pulmonary arterial pressure. Both, in dogs before and after the induction of heart failure, the new peptide led to a significant increase of urine flow and sodium and chloride excretion. In healthy dogs there were indirect indications for a small inhibitory effect on renin and aldosterone secretion. Thus, in contrast to the considerable attenuation of renal effects of ANP-(99-126) in heart failure, the efficacy of ANP-(95-126) on renal excretory function is well preserved, which may be because of the lack of proteolytic degradation in the kidney. These results suggest that ANP-(95-126) may have clinical implications for the treatment of patients with congestive heart failure.

Animals↗
PubMed1990

Endogenous natriuretic peptides: effect on collecting duct function in rat kidney.

In vivo microcatheterization of the medullary collecting duct of rat kidney was used to compare the functional effects of intravenous infusion of rat atrial natriuretic factor, human urodilatin (a peptide produced in the kidney), or porcine brain natriuretic peptide. All three peptides resulted in striking and quantitatively similar inhibition of NaCl and water reabsorption in the duct. In addition, all three induced significant K+ secretion in this part of the nephron. These results could not be explained by functional alterations in upstream tubular segments. We conclude that the three peptides are equivalent in their transport effects on the inner medullary collecting duct system, when administered at the same (presumably supramaximal) dose.

Animals↗
PubMed1990

Urodilatin, a natriuretic factor from kidneys, can modify renal and cardiovascular function in men.

Urodilatin is a newly identified analogue of human atrial natriuretic factor-(99-126) [ANF-(99-126)], which has recently been isolated from human urine and has 32 amino acid residues [ANF-(95-126)]. To investigate renal and cardiovascular effects in men, eight healthy subjects received injections of 25, 50, and 100 micrograms urodilatin iv compared with 50 micrograms ANF-(99-126) and placebo. Blood pressure decreased (P less than 0.05) after 50 micrograms ANF-(99-126), whereas urodilatin lowered diastolic blood pressure only at the highest dose (P less than 0.01). Heart rate increased (P less than 0.05-0.01) dose dependently after urodilatin injections. Glomerular filtration rate rose after 100 micrograms (from 120 +/- 3 to 156 +/- 7 ml.min-1.1.73 m-2, P less than 0.001) and 50 micrograms urodilatin (from 116 +/- 7 to 149 +/- 13 ml.min-1.1.73 m-2, P less than 0.01) but not after 25 micrograms urodilatin, ANF-(99-126), or placebo. Effective renal plasma flow was not significantly modified. Diuresis and excretion of sodium, chloride, and guanosine 3',5'-cyclic monophosphate increased (P less than 0.001) dose dependently; effects of 25 micrograms urodilatin equaled those of 50 micrograms ANF-(99-126). Plasma renin, aldosterone, and catecholamines were unchanged. We conclude that urodilatin can acutely modify renal and cardiovascular function in men and seems to exert more potent renal effects than ANF-(99-126).

Adult↗
PubMed1989

Phosphorylation and dephosphorylation of the natriuretic peptide urodilatin (CDD-/ANP-95-126) and the effect on biological activity.

Urodilatin (CDD-/ANP-95-126), a new peptide hormone from human urine, is comprised of the same amino acid sequence as cardiodilatin (CDD-99-126/alpha-hANP) except for N-terminal extention by four amino acid residues. The presence of the recognition sequence Arg101-Arg-Ser-Ser104 for the cyclic AMP-dependent protein kinase enables rapid phosphorylation in the Ser104-position. Phosphorylation of urodilatin is associated with decreased vasorelaxant potency, while dephosphorylation of "phospho-urodilatin" by acidic phosphatase completely restores bioactivity.

Acid Phosphatase↗
PubMed1989

Atrial myoendocrine cells (cardiodilatin/atrial natriuretic polypeptide-containing myocardiocytes) are target cells for estradiol.

Atrial myoendocrine cells of rat were investigated regarding estradiol uptake. It was found that, in addition to their specific endocrine function of producing cardiac polypeptides of the cardiodilatin/atrial natriuretic peptide (CDD/ANP) family, these cells also specifically accumulate radiolabeled estradiol. This co-localization supports the view that steroid hormones play an important role in the regulation of the CDD/ANP gene.

Animals↗
PubMed1989

The heart is the center of a new endocrine, paracrine, and neuroendocrine system.

This review indicates that the heart is a polypeptide-producing organ which should be classified among the traditional endocrine tissues. Cardiac hormones have only been known for a few years, the discovery of their endocrine functions, however, occurred in the 1950ies when Gauer, Henry and Kisch observed specific physiological and morphological features of the heart atria indicative of an endocrine activity. Because of their basic effects many target organs involved in the regulation of body fluid pressure and composition are related to this endocrine organ located in the atrial appendages of the heart. The compact endocrine portion of the heart is built up by myoendocrine cells which form the functional endocrine units and produce a variety of polypeptide hormones called cardiodilatin (CDD) or atrial natriuretic polypeptide (ANP), which belong to one family. Also, co-storage of a partially homologous regulatory polypeptide called brain natriuretic polypeptide (BNP) occurs, as has been determined by immunohistochemistry and radioimmunoassay. CDD and/or BNP are found in numerous organs where they exert paracrine and neurocrine functions, e.g., in the brain, peripheral nervous system, kidney, and adrenal medulla. In these organs, a differential post-translational processing of cardiac polypeptides is observed, resulting in different functional activities according to discriminating receptor interactions and degrading metabolism. Some of the extra-auricular sites of synthesis and storage of CDD-like peptides are briefly mentioned. In summary the heart constitutes the center of a multilocal and multifunctional system of specific cardiac polypeptides of endocrine, paraneuronal, and neuronal character.

Animals↗
PubMed1988

Neuropeptide (neuropeptide Y, neurotensin, vasoactive intestinal polypeptide, substance P, calcitonin gene-related peptide, somatostatin) immunohistochemistry and ultrastructure of renal nerves.

With the use of several region-specific antisera and the peroxidase-antiperoxidase (PAP) technique, several regulatory polypeptides were localized in nerves of the kidney. Neuropeptide Y (NPY)- immunoreactivity (IR), neurotensin (NT)-IR and vasoactive intestinal polypeptide (VIP)-IR occurred at high densities in all segments of the renal arterial system forming a perivascular plexus. Furthermore, NT-IR nerves were particularly frequent at the juxtaglomerular apparatus (JGA). Calcitonin gene-related peptide (CGRP)-IR was mainly concentrated in nerves supplying the hilus arteries and the JGA. Substance P (SP)-IR was predominantly found in large varicosities close to large renal arterial vessels and in the vicinity of the JGA. Somatostatin (SOM)-IR was only observed in single varicosities located at the media-adventitia border of large renal hilus arteries. The peptidergic nerves are correlated to their ultrastructural counterpart. In addition, the distribution patterns and the frequency of the different types of renal peptidergic nerve fibres are evaluated and compared. The functional role of these neuropeptides and their origin within the efferent branch of this part of the peripheral autonomic nervous system is discussed. Furthermore, the implication of some of the neuropeptides studied in afferent renal innervation is also substantiated.

Animals↗
PubMed1986

Peptidergic innervation of the human and guinea pig uterus.

The peptidergic innervation of the human and guinea pig uterus was studied using immunohistochemical methods. Antibodies against several peptides were applied for the PAP-technique to stain peptidergic nerves specifically. These are located in the adventitia of large uterine vessels in the myometrium and smaller vessels of the myometrium and endometrium. A differential distribution of the individual peptides was observed for VIP-IR (vasoactive intestinal polypeptide immunoreactivity), NPY-IR (neuropeptide Y), SP-IR (substance P), SOM-IR (somatostatin) and NT-IR (neurotensin) nerve fibers. Specific functional implications for these neuropeptides can be derived from their histochemical location.

Animals↗