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Biomedical subjects

R E Lang

Publications and source records attributed to R E Lang.

At least 127 records · Page 7Linked to original sources
PubMed1985

Atrial natriuretic peptide in plasma of volume-overloaded children with chronic renal failure.

The effect of volume changes on the plasma concentration of atrial natriuretic peptide (ANP) in children with chronic renal failure was investigated by the use of a specific and sensitive radioimmunoassay. Predialysis plasma ANP was significantly higher in children with end-stage renal disease than in healthy children and children with advanced renal failure without evidence of volume expansion. During haemodialysis plasma ANP decreased significantly and plasma renin activity rose slightly, whereas plasma arginine vasopressin and aldosterone did not change. Plasma ANP correlated positively with volume status (body weight gain during the interval between two haemodialysis sessions). An expanded extracellular fluid volume thus seems to be a major stimulus for the rise in ANP in children with end-stage renal disease. The findings suggest that ANP may be important in volume homoeostasis.

Adolescent↗
PubMed1985

Effects of converting enzyme inhibitors: ramipril and enalapril on peptide action and sympathetic neurotransmission in the isolated heart.

The role of converting enzyme (CE) in heart function was studied by assessing the inhibition of CE activity in rat heart tissue and in isolated perfused hearts from rat, guinea-pig and rabbit (Langendorff technique). Angiotensin I (ANG I) added to the perfusate reduced coronary flow (FLO) in all species, increased force of contraction (CON) in rats, decreased CON in guinea-pigs and had no effect on CON in rabbits. In contrast, bradykinin (BK) increased FLO in all species, decreased CON in rats, increased CON in guinea-pigs and had no effect on CON in rabbits. The CE inhibitors ramipril (HOE498) 1 mg/kg and enalapril (MK421) 30 mg/kg given orally 1 h prior to killing of the animals inhibited the ANG I effects and potentiated the BK effects but had no effects on the action of ANG II. The same doses of the two CE inhibitors produced up to 24 h inhibition of CE activity measured biochemically in the heart after single oral doses. Electrical sympathetic stimulation of the cardiac nerves (SNS) in isolated rabbit heart resulted in an increase of HR and CON and in an initial decrease and subsequent increase of FLO. The effects of SNS on HR and FLO were significantly reduced following HOE498 (1 mg/kg) pretreatment. The results suggest that local CE is involved in the regulation of peptide effects in the heart, including the ANG II-mediated facilitation of neurotransmission.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

The cardiovascular effects of oxytocin in conscious male rats.

In conscious, chronically instrumented normotensive male Wistar rats intravenous (i.v.) administration of oxytocin (OXT) (greater than or equal to 100 ng) induced a dose-related biphasic change in mean arterial pressure (MAP). This consisted of an initial pressor effect accompanied by bradycardia and a decrease in cardiac output (CO), followed by a more prolonged fall in MAP which reached a maximum 30 min after injection and was accompanied by an increase in CO. The more specific (Thr4,Gly7]OXT analogue (0.01-10 micrograms i.v.) caused a dose-related fall in MAP and a rise in CO which reached a maximum after 15-30 min. Similarly in spontaneously hypertensive rats of the stroke prone strain (SHRSP) an initial pressor effect and delayed fall in MAP were apparent after OXT (0.1 and 10 micrograms i.v.) only the decrease in MAP being evident with the [Thr4,Gly7]OXT analogue. These responses were significantly larger than those observed in Wistar Kyoto controls. The pressor effects are therefore interpreted to be due to vasopressin receptor activation while the depressor effects appear to be oxytocin specific. In sinoaortic denervated rats, OXT (0.1 and 10 micrograms i.v.) induced an enhanced initial pressor effect with a much reduced reflex bradycardia and fall in CO. A larger and more prolonged delayed fall in MAP was apparent with both OXT and [Thr4,Gly7]OXT accompanied by a decrease in CO when compared to sham-operated controls. Intracisternally (i.c.) administered OXT (0.05-10 ng) had no effect on MAP or heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Localization of renin (EC 3.4.23) and converting enzyme (EC 3.4.15.1) in nerve endings of rat brain.

Synaptosomes and lysosomes of rat brain were separated by differential centrifugation and a two-step gradient centrifugation with colloidal silica-gel (Percoll). The organelles were identified by the measurement of established marker-enzymes and by electronmicroscopy. Renin activity, measured by radioimmunoassay for angiotensin I (ANG I), was localized in the synaptosomes and cathepsin D-activity was found in the lysosomal fraction. Converting-enzyme activity was present in the renin-containing synaptosomes. Part of the brain renin activity could be activated by pre-incubation with trypsin. Affinity chromatography of an organelle-enriched brain fraction was carried out using a caseinyl-sepharose column and resulted in the separation of renin from cathepsin D activity; the renin peak was inhibited by antibodies raised against rat kidney renin. We conclude, that the formation of ANG I and its activation to angiotensin II (ANG II) by converting enzyme is possible in synaptosomes. This adds further evidence to an intraneuronal synthesis of ANG I and ANG II in the brain and is in support of previous results demonstrating an intraneuronal localization of the components of the brain renin-angiotensin system.

Animals↗
PubMed1985

Vasopressin--oxytocin in cerebrospinal fluid of schizophrenic patients and normal controls.

Vasopressin and oxytocin seem to be involved in the processes of learning and memory in animals and probably in man. These peptides appear to have opposite effects in that vasopressin improves memory processes and oxytocin produces amnestic effects. We measured these neuropeptides in the cerebrospinal fluid of schizophrenic patients with and without neuroleptic treatment, psychiatrically healthy controls and drug-free patients before and after three weeks' neuroleptic treatment. There were no significant differences in vasopressin concentrations between schizophrenics and controls. No influence of neuroleptic treatment on vasopressin concentrations was detected. In contrast, concentrations of oxytocin were increased in all schizophrenic patients and were higher in those receiving neuroleptic treatment. In addition, oxytocin concentrations increased after three weeks' neuroleptic treatment. Drug-induced increase of oxytocin concentrations may be of significance in the clinically observed amnestic syndromes and debilitation in schizophrenics treated with neuroleptics.

Adult↗
PubMed1985

Altered neuropeptide concentrations in spontaneously hypertensive rats: cause or consequence?

Changes in brain neuropeptide content in spontaneously hypertensive rats may be primarily related to the development of hypertension or may be secondary consequences of it. We have measured brain concentrations of beta-endorphin, Leu-enkephalin, arginine vasopressin (AVP) and oxytocin (OXT) in stroke-prone spontaneously hypertensive rats (SHRSP) and in age-matched normotensive Wistar Kyoto (WKY) controls, as well as in SHRSP with normalized blood pressure by chronic treatment with clonidine. Opioid peptide contents were measured in 12-, 18- and 24-week-old rats. beta-Endorphin was measured in the neuro-intermediate and anterior lobes of the pituitary, the hypothalamus, mid-brain and brain stem; Leu-enkephalin in the neuro-intermediate lobe of the pituitary, hypothalamus, mid-brain, brain stem, as well as in the spinal cord and adrenal glands. AVP and OXT were measured in the neuro-intermediate lobe of the pituitary, hypothalamus, brain stem and spinal cord. beta-Endorphin in the neuro-intermediate lobe of the pituitary was significantly higher in 12- and 18-week-old SHRSP. Adrenal gland Leu-enkephalin was lower in SHRSP as compared with the WKY. OXT and AVP contents were markedly reduced in all brain regions of SHRSP except the neuro-intermediate lobe of the pituitary, where no significant changes were found. In no case did long-term antihypertensive treatment with clonidine reverse the altered peptide content in the SHRSP. We conclude that alterations in brain neuropeptide content in SHRSP are not secondary to hypertension. The blood pressure lowering activity of clonidine appears not to depend on major alterations of peptide concentrations. A genetic defect in the synthesis of adrenal enkephalins and hypothalamic OXT and AVP seems likely from these studies.

Animals↗
PubMed1985

Biochemical and immunological evidence for a cardiodilatin-like substance in the snail neurocardiac axis.

Cardiac hormones, which have been isolated recently from mammalian atria, are potent regulatory peptides of blood pressure and blood volume. By using biochemical and immunological methods to determine cardiac hormones of the cardiodilatin family, this type of peptide hormone was detected in a neurosecretory system projecting from the subesophageal ganglion to the heart of the snail. The cardiodilatin-like molecule was characterized by its biological effects on mammalian vascular smooth muscle, by radioimmunoassay combined with high-performance liquid chromatography, and by immunocytochemistry. In mammals cardiodilatin-like peptides appear to serve purely endocrine functions. In contrast, in the snail they are present in a neuroendocrine system, the function of which remains to be established.

Animals↗
PubMed1985

Differential effects of central angiotensin II and substance P on sympathetic nerve activity in conscious rats. Implications for cardiovascular adaptation to behavioral responses.

The centrally induced effects of angiotensin II and substance P on the cardiovascular system and on neuronal efferent activity of the splanchnic, renal, and adrenal nerves were investigated in chronically instrumented conscious rats. The pressor responses to substance P injected into the lateral brain ventricle were accompanied by marked and short latency increases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a rise in plasma noradrenaline and adrenaline. Behaviorally, an arousal-type reaction was observed. In contrast, the pressor responses to intracerebroventricular angiotensin II were associated with initial decreases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a fall in plasma noradrenaline at the time of the maximal blood pressure increase. In some but not all animals, a second blood pressure peak associated with increases in heart rate and splanchnic nerve activity was observed after several minutes. Incomplete chronic sinoaortic baroreceptor deafferentiation prevented the angiotensin II-induced fall in heart rate but not the initial fall in splanchnic nerve activity. The decreases in splanchnic nerve activity also occurred in diabetes insipidus rats and persisted in Long Evans rats after vascular vasopressin receptor blockade with d(CH2)5AVP, despite marked reductions of the pressor responses in both groups. Peripheral alpha-adrenoceptor blockade with prazosin or ganglion blockade with hexamethonium inhibited the central angiotensin II pressor responses only in combination with vasopressin receptor blockade. On the other hand, either sympatholytic drug, alone, abolished the pressor responses in the diabetes insipidus rats. This indicates that in intact conscious rats the central pressor effects of angiotensin II are initiated by vasopressin release but become dependent on the sympathetic nervous system when vasopressin is absent or not effective. When rats were allowed to drink in response to angiotensin II, a further sharp rise in blood pressure occurred, together with increases in heart rate and splanchnic nerve activity. The results demonstrate fundamental differences in the mechanisms by which central pressor peptides can influence cardiovascular and autonomic function. It is conceivable that the distinct sympathetic response patterns to central angiotensin II and substance P receptor stimulation form part of a specific cardiovascular adjustment to the individual behavioral reactions, such as drinking, as in the case of angiotensin II, or arousal within the central processing of pain, as in the case of substance P.

Action Potentials↗
PubMed1985

Atrial natriuretic factor stimulates renin release from the isolated rat kidney.

Intrarenal infusion of atrial natriuretic factor has been reported to increase renal blood flow and sodium excretion, and either to depress or not to affect renin release. We examined the effect of a synthetic atrial peptide, AP II, on renin release, renal perfusate flow and glomerular filtration rate in isolated rat kidneys, perfused at constant pressure with a synthetic Krebs-Henseleit hydroxyethyl-starch-albumin medium. Atrial peptide II, 0.3 to 30 nmol/l, produced a concentration-dependent increase in renin release. Renal perfusate flow increased initially but returned to pre-infusion levels during infusion. During vasodilatation by continuous infusion of hydralazine, AP II produced only minor changes of perfusate flow but higher increases of renin release than in controls, indicating that this effect is not secondary to vasodilatation. During suppression of prostaglandin synthesis by indomethacin, the effects of AP II were unaltered. Furthermore, AP II in concentrations up to 200 nmol/l did not alter resting membrane potential in juxtaglomerular cells.

Animals↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

[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↗