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D Ganten

Publications and source records attributed to D Ganten.

At least 379 records · Page 21Linked to original sources

Combined high-performance liquid chromatography-radioimmunoassay for the characterization and quantitative measurement of neuropeptides.

A method for the extraction, separation, characterization and quantitation of angiotensins, opioid peptides and several other neuropeptides in biological samples is described. Gradient elution in different reversed-phase high-performance liquid chromatographic systems gives high resolution with constant recoveries between 60 and 70%, allows UV detection at 220 nm and is compatible with radioimmunoassay. The method is highly reproducible and applicable to the characterization and quantitative measurement of peptides in the femtomolar range. The practicability of the method is demonstrated for angiotensin peptides in plasma, brain and peripheral organs, as well as for opioid peptides in the heart.

Angiotensin I↗

Angiotensin II immunoreactivity in the neural afferents and efferents of the subfornical organ of the rat.

Angiotensin II (AII) immunoreactive cells and fibers were identified in the subfornical organ (SFO) of the rat. Cells were distributed in an annulus around the periphery of the SFO and were most visible in the Brattleboro rat treated with colchicine. Fibers were observed in a plexus, located centrally within the ring of cells, and knife-cuts suggested that they arise from parent cell bodies lying outside of the SFO. Studies combining immunohistochemistry with retrograde transport identified the perifornical zone of the lateral hypothalamus, the rostral zona incerta, and the nucleus reuniens of the thalamus as the source of AII-stained inputs to the SFO, and the region of the median preoptic nucleus as a recipient of AII-immunoreactive SFO efferents. It is suggested that these biochemically defined connections of the SFO participate in the central neural control of fluid balance.

Amidines↗

Distribution of neurophysin II immunoreactive nerve fibers within the subnuclei of the nucleus of the tractus solitarius of the rat.

The location of neurophysin II immunoreactive nerve fibers and preterminal processes has been examined in various functionally distinct subnuclei of the nucleus of the tractus solitarius (nTS) using the indirect immunofluorescence method for immunocytochemistry combined with cytoarchitectonic identification. The nTS is responsible for integrating respiratory and autonomic reflex activity: the vlnTS, vnTS, ni and nI are associated with respiratory activity; the dlnTS and dnTS are important sites for the integration of baroreceptor and chemoreceptor activity; the ncom, dnTS and dlnTS integrate cardiac afferent activity and the mnTS mediates both cardiovascular and gastrointestinal effects. At levels caudal to the obex, the ncom contained the largest number of neurophysin II immunoreactive nerve fibers and the mnTS and dmnX contained moderate neurophysin II immunoreactivity. At levels rostral to the obex the region of the dorsal medulla adjacent to the mnTS and dnTS (PVR and dPSR) showed the densest immunoreactivity and the mnTS, dmnX and vPSR showed moderate immunoreactivity. At the rostral pole of the nTS, neurophysin II immunoreactive nerve terminals were seen in the dendritic regions of cells in dmnX and mnTS. This selective distribution of neurophysin II immunoreactive nerve terminals in the cardiovascular and gastrointestinal subnuclei of the nTS implicates a direct, descending, hypothalamic, oxytocin-neurophysin II containing pathway interacting with these nTS functions. These results confirm the hypothesis (Sawchenko and Swanson) that descending neurophysin II immunoreactive pathways represent an important neuronal system for the hypothalamic regulation of cardiovascular (vasomotor) and gastrointestinal nuclei in the brainstem.

Animals↗

[The central nervous system, regulation of blood pressure and hypertension. Recent advances in the role of the central nervous system in the regulation of blood pressure].

Evidence for a contribution of the central nervous system to the development and maintenance of high blood pressure disease is accumulating. Increased activity of the sympathetic nervous system has been demonstrated experimentally and clinically. Centrally acting drugs such as a-methyldopa, clonidine or reserpine effectively lower blood pressure. CNS dysregulation, as seen by alterations in neurotransmitter concentrations or baroreceptor reflex function, have been detected in early stages of hypertension. In animal experiments renal hypertension could be prevented by central chemical sympathectomy. Finally, psychosocial stress can induce sustained hypertension and a relationship between personality pattern, conflict behaviour and high blood pressure has been established.

Animals↗

Angiotensin stimulates beta-endorphin release from anterior pituitary gland cell cultures of rats.

The effect of exogenous and locally generated angiotensin II (ANG II) on the release of beta-endorphin (beta-END) from anterior pituitary cell cultures of rats was studied. Angiotensin I (ANG I) and ANG II stimulated the release of beta-END, the ANG I effects being inhibited by addition of the converting enzyme inhibitor captopril. Renin and angiotensinogen had no effect when given separately, but their combination increased beta-END release. Thus ANG II causes the release of beta-END, but the putative pituitary renin system cannot be stimulated by exogenous renin or angiotensinogen; converting enzyme, however, acts locally to produce biologically active ANG II from ANG I.

Angiotensin I↗

Distribution of neuropeptide immunoreactive nerve terminals within the subnuclei of the nucleus of the tractus solitarius of the rat.

The location of substance P, enkephalin and somatostatin (SRIF), and neurophysin II immunoreactive nerve terminals and preterminal processes in the caudal part of the nucleus of the tractus solitarius (nTS) was examined by the indirect immunofluorescence method for immunocytochemistry combined with cytoarchitectural identification of nuclear subgroups in the same tissue. In 22 Sprague-Dawley rats we examined 14-micrometers-thick serial sections of the dorsal medulla at levels from 1 mm caudal to 2 mm rostral to the obex. These sections were incubated with substance P, enkephalin, somatostatin, and neurophysin II antisera. All four peptides were examined in each case and five typical levels (two caudal and three rostral to the obex) were selected for comparison of terminal distribution between peptides. All sections were photographed under the fluorescence microscope and then counter-stained with cresyl violet. This method of analysis revealed distinct patterns of neuropeptide immunoreactivity in the subnuclei of the nTS that varied according to the level of the section. The nTS is responsible for integrating respiratory, cardiovascular (baroreceptor and cardiac), and gastrointestinal functions. The ventrolateral subnucleus (Vl)nTS, ventral subnucleus (v)nTS, interstitial subnucleus (ni)nTS, and intermediate subnucleus (nI)nTS are the major respiratory subnuclei with vlnTS and vnTS prominently associated with pulmonary afferents, ni associated with laryngeal afferents, and nI with tracheal afferents. The vlnTS, vnTS, and ni showed a moderate density of somatostatin-positive nerve terminals, scattered substance P and enkephalin immunoreactivity, and no neurophysin II-positive terminals. The nI showed moderate density of substance P immunoreactive nerve terminals. The subnuclei of the nTS receiving baroreceptor and chemoreceptor afferents--dorsolateral and dorsal (dl and d) subnuclei of nTS--showed scattered substance P immunoreactive nerve terminals. The commissural nucleus of nTS (ncom), which receives most of the cardiac afferents, showed a moderate density of enkephalin-positive immunoreactive nerve terminals. The medial subnucleus (m)nTS at levels rostral to the obex, the primary site for the termination of gastrointestinal afferents, showed substance P immunoreactivity in moderate amounts and weak immunoreactivity for all the other neuropeptides. An important result of these experiments was the observation that regions of the medulla adjacent to the nTS, i.e., the ventral parasolitarius region (vPSR), dorsal (d)PSR, and the periventricular region (PVR) showed the densest amounts of immunoreactive nerve terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Coexistence of renin and angiotensin II in epitheloid cell secretory granules of rat kidney.

The distribution of renin and angiotensin II (ANG II) in juxtaglomerular epitheloid cells of control and adrenalectomized rats was studied, using specific antisera and the protein A-gold technique in Lowicryl- and glycol methacrylate-embedded tissue. The matrix of virtually all mature secretory granules of epitheloid cells contains not only renin, but also ANG II. On adrenalectomy, the concentration of both renin and On adrenalectomy, the concentration of both renin and ANG II in the granule internum increases markedly, as indicated by the density of the immunolabel. Given the coexistence of renin and ANG II in the granule matrix, it is quite probable that, with each secretory event, a certain amount of ANG II is released together with renin. Further experiments will have to show if this amount of ANG II cosecreted with renin is sufficient to elicit immediate local intrarenal actions. ANG I, as well as angiotensinogen and converting enzyme, were not found in epitheloid cells. It is therefore inferred that ANG II is not generated intracellularly, but within the extracellular space and subsequently taken up by pinocytosis and incorporated into the secretory granules of epitheloid cells.

Adrenalectomy↗

Release of opioid peptides in canine hemorrhagic hypotension: effects of naloxone.

Sixteen anesthetized foxhounds were instrumented for hemodynamic measurements. The adrenolumbar vein was cannulated, and hemorrhagic hypotension (MAP = 40 mmHg for 3h) was induced by bleeding. The plasma levels of beta-endorphin (beta-END), methionine-enkephalin (M-ENK), and leucine-enkephalin (L-ENK) were determined in systemic and adrenal venous blood by specific RIA. Five dogs received an i.v. bolus of naloxone (2 mg/kg) and a subsequent naloxone infusion of 2 mg/kg per hour 1 h after onset of hypovolemia. Eleven dogs served as controls and received equivalent volumes (1 ml/kg per hour) of saline. Hemorrhage resulted in a sharp increase in plasma concentrations of all measured opioid peptides, particularly of M-ENK (26-fold) and L-ENK (24-fold) in the adrenal effluent. Systemic beta-END levels remained 3-fold increased, whereas the ENK release decreased spontaneously. Naloxone treatment inhibited the spontaneous fall of adrenal ENK release during the hypotensive phase; the ENK values remained elevated 20- to 35-fold. Reinfusion of the autologous blood resulted in a normalization of the concentrations of all peptides in both groups. These data demonstrate that hemorrhagic hypotension will cause stimulation of release of endogenous opioid peptides. The high levels of ENK in the adrenal effluent indicate that the adrenal gland is the main source of these peptides in the circulation. In addition to beta-END, the ENK have therefore to be considered as possible factors perpetuating circulatory shock.

Adrenal Glands↗

The renal kallikrein-kinin system in spontaneously hypertensive rats.

In male spontaneously hypertensive rats (SHRSP) of the stroke prone strain (Okamoto) and in normotensive Wistar-Kyoto rats (WKY) urinary kallikrein excretion was investigated at different age and at drug-induced diuresis. In rats of both strains from 7th till 19th week of age urinary kallikrein excretion increased with age. In SHRSP of 7th till 11th week of age kallikrein excretion was higher than in WKY rats, while it was lower in the 48-week-old SHRSP. No correlation was found between urinary kallikrein excretion and systolic blood pressure. In SHRSP and WKY rats a similar daily rhythm of kallikrein excretion in urine was found being high in the early morning and low in the afternoon. Kallikrein excretion correlated significantly with urine volume. The loop diuretic bumetanide (4 and 40 mg/kg) induced diuresis and natriuresis in both strains, however more marked in the WKY rats than in the SHRSP. Urinary kallikrein excretion, however, showed in both strains the same biphasic course with a short lasting increase and a secondary decrease. Thus, in the average urinary kallikrein excretion was not effected by the drug. Prolonged treatment with furosemide over 5 days (125 mg/kg) resulted in an increase in kallikrein excretion in urine, more pronounced in the WKY rats than in the SHRSP. The observed results suggest that renal kallikrein-kinin system is not involved in the development of spontaneous hypertension as a pathogenetic factor, but rather is influenced by other factors like hormone interactions, i.e. mineralocorticoids and catecholamines, as well as renal function and acute changes in urine flow.

Angiotensin II↗

Antihypertensive effect of the GABA receptor agonist muscimol in spontaneously hypertensive rats. Role of the sympathoadrenal axis.

The antihypertensive action of central GABA-ergic stimulation was investigated in conscious stroke prone spontaneously hypertensive rats. Injection of the potent GABA agonist muscimol (0.01-1 microgram) into the lateral brain ventricle (icv) lowered mean arterial blood pressure (192.1 +/- 8.4 mm Hg) dose-dependently in stroke prone spontaneously hypertensive rats with a maximal fall of -52.7 +/- 5 mm Hg lasting for about 90 minutes. This was accompanied by bradycardia and sedation. Pretreatment with atropine (2 mg/kg, ip, or 15 micrograms/kg, icv) did not significantly influence the muscimol-induced fall in mean arterial pressure. In normotensive (109.3 +/- 1.9 mm Hg) Wistar-Kyoto controls, the maximal decrease in mean arterial pressure was -12.1 +/- 1.6 mm Hg from 109.3 +/- 1.9 mm Hg, and the duration of the effect was much less than in stroke prone spontaneously hypertensive rats, Following 1 microgram muscimol, icv, plasma noradrenaline did not fall significantly in stroke prone spontaneously hypertensive and Wistar-Kyoto rats, but in stroke prone spontaneously hypertensive rats, plasma adrenaline was fully suppressed (from 118.1 +/- 24.2 to 22.8 +/- 5.7 pg/ml) throughout the depressor response. The efferent sympathetic nervous activity as directly recorded from the n. splanchnicus was similar in conscious stroke prone spontaneously hypertensive and Wistar-Kyoto rats, and was moderately reduced in both strains by 1 microgram muscimol, icv.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗