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Biomedical subjects

R E Lang

Publications and source records attributed to R E Lang.

At least 37 records · Page 2Linked to original sources

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↗

Neuropeptide Y mRNA regulation in rat sympathetic ganglia: effect of reserpine.

To study the mechanism underlying trans-synaptic neuropeptide regulation, mRNA levels of neuropeptide Y were examined in the rat stellate and superior cervical ganglia using a specific neuropeptide Y cRNA probe. Basal levels of neuropeptide Y mRNA were detectable in total RNA extracts from single ganglia. Reserpine induced a large rise in ganglion neuropeptide Y mRNA. Decentralization prevented the increase of neuropeptide Y mRNA content in the ganglia. This suggests that the reserpine induced increase in neuropeptide Y mRNA was dependent on transsynaptic stimulation. Consequently, neuropeptide mRNA levels in sympathetic ganglia may be under the control of preganglionic impulse flow.

Autonomic Fibers, Preganglionic↗

Identification of a receptor protein for neuropeptide Y in rabbit kidney. G-protein association and inhibition of adenylate cyclase.

We previously identified the receptor for neuropeptide Y (NPY) on rabbit kidney membranes as a 100 kDa protein [(1990) J. Biol. Chem. 265, 18142-18143]. It is demonstrated in this study that the stable guanine nucleotide analogue, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), is capable of decreasing the labeling of the 100 kDa protein in a concentration-dependent manner, with an IC50 value of 50 microM. This suggests that the 100 kDa protein represents a G-protein coupled receptor type. In isolated proximal tubules from rabbit kidney NPY decreases the parathyroid hormone stimulated cAMP production in a dose-dependent fashion. This indicates that the NPY receptor in rabbit kidney is negatively coupled to adenylate cyclase by a G1-like protein.

Adenylyl Cyclases↗

Atrial natriuretic peptide (ANP) in patients with chronic renal failure on maintenance haemodialysis.

Atrial natriuretic peptide (ANP), a recently discovered cardiac hormone, is an important regulator of body fluid homeostasis. Twenty patients with established chronic renal failure and on maintenance haemodialysis were studied before and after dialysis with capillary dialysers. ANP was determined by RIA after extraction. Mean (+/- SD) pre-dialysis ANP concentration was 146 +/- 51 pg/ml and decreased significantly during dialysis to 68 +/- 38 pg/ml (p less than 0.001). Per cent and absolute changes in plasma ANP level correlated significantly with concomitant changes in body weight (r = 0.764; p less than 0.001 and r = 0.558; p less than 0.01, resp.) but not with changes in serum creatinine, blood pressure or serum electrolytes. The obtained results indicate that ANP levels in patients with chronic renal failure are elevated mainly due to fluid overload, and the rapid fall in ANP concentration observed during haemodialysis is caused by the removal of excess fluid from the body.

Adult↗

The role of neuropeptides in cardiovascular regulation.

During the past few years more than 30 novel, biologically active peptides have been discovered. Some are produced in endocrine glands and circulate as hormones in the blood; others are contained in the enterochromaffin cells of the gut and may be involved in the regulation of intestinal functions. The vast majority of new peptides, however, have been detected in the central and peripheral nervous systems, where they are synthesized in distinct neurons and stored in neurovesicles. Many of these neuropeptides may be involved in circulatory regulation. There is evidence supporting such a role, especially for centrally located angiotensin, opioid peptides, substance P, neuropeptide Y (NPY), vasopressin, atrial natriuretic peptide (ANP), kinins, corticotropin releasing factor, bombesin, and somatostatin. In this review we discuss the cardiovascular actions of angiotensin, neuropeptide Y, and calcitonin gene related peptide.

Angiotensin II↗

Effects of saline loading during head down tilt on ANP and cyclic GMP levels and on urinary fluid excretion.

In the present study the renal and humoral effects of acute saline infusions were investigated in six healthy male volunteers before, during and after a ten day period of -6 degrees head-down-tilt (HDT). During the whole 23-day study period the subjects received a standardized diet including 40 ml water and 125 mg NaCl per kg body weight per day. After the infusion of 0.9% saline (22 ml/kg within 20 minutes) plasma atrial natriuretic peptide (ANP) levels were only slightly increased (not significant) at the end of the infusion, while plasma cyclic GMP levels were significantly increased by about 40% (p<0.05) one hour later. No difference was observed in the plasma ANP and cyclic GMP changes between the pre-HDT, the HDT and the post-HDT infusion experiment. Urine flow, sodium excretion and urinary cyclic GMP excretion were significantly increased (p<0.05 and below) by 100 to 300% during the second and third hour after each saline infusion. However, during these short-term periods only 20% of the infused water and less than 20% of the infused sodium were excreted. Furthermore, a significantly increased volume, sodium and cyclic GMP excretion was observed for over 48 hours after each fluid load experiment. These data suggest that HDT does not induce major alterations in the regulation of an acute saline infusion and plasma ANP does not play a major role in the diuretic/natriuretic effects of volume loading.

Adult↗

Transcription, storage and release of atrial natriuretic factor in the failing human heart.

1. In this study the relationship between the synthesis of atrial natriuretic factor at the level of atrial natriuretic factor mRNA and the atrial storage and circulating plasma levels of atrial natriuretic factor were investigated in 15 patients with heart failure. The patients underwent right and left heart catheterization before cardiac surgery for valve replacement or coronary artery bypass grafting. 2. Plasma concentrations of atrial natriuretic factor were correlated to atrial levels of atrial natriuretic factor mRNA. Atrial levels of atrial natriuretic factor mRNA and plasma concentrations of atrial natriuretic factor exhibited a close correlation to both pulmonary artery pressure and left atrial pressure. No relationship, however, could be found between the right atrial content of atrial natriuretic factor and both the expression of atrial natriuretic factor mRNA in the atria and the plasma levels of atrial natriuretic factor. 3. From these data it may be concluded that increased plasma levels of atrial natriuretic factor in the pressure- and/or volume-overloaded heart are associated with an elevated level of atrial natriuretic factor mRNA. We suggest that not only plasma levels of atrial natriuretic factor but also the expression of atrial natriuretic factor in the atrial are related to left ventricular filling pressures in the failing human heart.

Atrial Natriuretic Factor↗

Solubilization and characterization of active neuropeptide Y receptors from rabbit kidney.

Active neuropeptide Y receptors were solubilized from rabbit kidney membranes using the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS). In membrane fragments and soluble extracts neuropeptide Y binding was time dependent, saturable, reversible, and of high affinity. Scatchard analysis of equilibrium binding data indicated a single class of binding sites with respective KD and Bmax values of 0.09 nM and 530 fmol/mg of protein for the membrane-bound receptors and 0.10 nM and 1585 fmol/mg of protein for the soluble receptors. Neuropeptide Y binding was specifically inhibited by the nonhydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) in a concentration-dependent manner, with IC50 values of 28 and 0.14 microM for membrane-bound and soluble receptors, respectively, suggesting that neuropeptide Y receptors are functionally coupled to GTP-binding regulatory proteins. Cross-linking studies were performed with the heterobifunctional N-hydroxysuccinimidyl-4-azidobenzoate and the monofunctional neuropeptide Y derivative, azidobenzoyl and led to the identification of a 100 kDa peptide that should represent the covalently labeled neuropeptide Y receptor.

Affinity Labels↗

Vasopressin mRNA in the neurolobe of the rat pituitary.

Pro-vasopressin-neurophysin mRNA (AVP mRNA) was assayed in the pituitary gland of rats from different strains, using a specific cRNA probe corresponding to exon C of the vasopressin gene. Northern blot analysis revealed the presence of an about 650 base pair (bp) AVP mRNA in the neurolobe of all strains. No signal was found in the anterior or intermediate lobes. Partial nucleotide sequence analysis suggested identity with the genuine AVP mRNA. Osmotic stimulation with 2% saline or water deprivation increased AVP mRNA levels in a fashion that paralleled changes seen in the hypothalamus. The origin of the AVP mRNA in the neurolobe is uncertain but is likely to be the pituicytes. Transport of the mRNA into the nerve endings of hypothalamic supraoptic and paraventricular neurons is an alternative possibility.

Animals↗

Plasma concentrations of atrial natriuretic peptide during physical exercise in patients with congestive heart failure.

Plasma concentrations of atrial natriuretic peptide (ANP) were measured in 25 patients with organic heart disease during physical exercise (baseline and maximum workload) in order to investigate if the responsiveness of stimulated release of ANP is still preserved in patients with heart failure and chronically elevated cardiac filling pressures. Since plasma concentrations of ANP are known to be positively correlated with mean right atrial pressures (RAP), the patients were divided into two groups according to their resting RAP; group I; those with normal RAP (less than or equal to 5 mmHg; n = 11); group II; those with elevated RAP (greater than 5 mmHg; n = 14). Under baseline conditions RAP (3.2 +/- 0.4 mmHg vs. 8.8 +/- 0.7 mmHg; p less than 0.01), pulmonary artery diastolic pressure (PADP; 9.5 +/- 0.9 mmHg vs. 17.9 +/- 1.8 pg/ml; p less than 0.01), and plasma ANP levels (128 +/- 19 pg/ml vs. 204 +/- 60 pg/ml; p less than 0.06) were significantly lower in group I than in group II. Both at rest and during maximum workload, plasma ANP concentrations were closely related to RAP, PADP, and mean pulmonary artery pressures in both groups. During exercise in all patients, RAP and PADP significantly increased, as well as plasma ANP concentrations. Similar increments in plasma ANP concentrations were accompanied by greater changes in RAP in group II than in group I. However, identical changes in PADP lead to identical increments in plasma ANP concentrations in both groups. In conclusion, the increments of plasma ANP concentrations during physical exercise were independent of the resting values of PADP, RAP, and plasma ANP concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Localization of atrial natriuretic peptide/cardiodilatin (ANP/CDD)-immunoreactivity in the lacrimal gland of the domestic pig.

The presence of atrial natriuretic peptic/cardiodilatin-immunoreactive material was demonstrated in the lacrimal gland of the domestic pig by high performance liquid chromatography and radioimmunoassay. The immunohistochemical localization revealed a distinct population of cuboid or spindle-shaped ANP/CDD-IR cells in the epithelium of the terminal portion of the secretory tubules. In addition, a moderate number of positive cells was localized intraepithelially in the intralobular ducts as well as the connective tissue between these ducts. Our findings provide a morphological indication that ANP/CDD may play a physiological role in the regulation of sodium transport and secretion in the lacrimal gland.

Animals↗

Detection of vasopressin mRNA in the neurointermediate lobe of the rat pituitary.

A messenger ribonucleic acid (mRNA) homologous to the transcript that encodes vasopressin (VP) was detected in the neurointermediate lobe (NIL) of the rat pituitary. The abundance of this transcript is approximately 1/100th the amount detected in the hypothalamus. In rats drinking 2% NaCl-water for 0,2,4, or 10 days, or for 10 days and then tap water for 14 days, the levels of VP mRNA in the NIL were altered in a fashion that paralleled changes in the hypothalamus.

Animals↗

Atrial natriuretic peptide mRNA in patients with heart disease.

The regulation of atrial natriuretic peptide (ANP) synthesis within cardiac atrial myocytes was investigated in 8 patients undergoing cardiac surgery (valve replacement or coronary bypass graft). Hemodynamic data were obtained during cardiac catheterization and venous plasma samples for ANP were withdrawn prior to surgery. Probes for determination of tissue ANP levels and ANPmRNA concentrations were taken from the right atrium. Both plasma ANP (r = 0.75; P less than .05) and ANPmRNA (r = 0.86; P less than .01) were closely related to mean pulmonary artery pressure. ANPmRNA was also related to plasma ANP (r = 0.60; P less than .07). However, no significant relationships were obtained between either plasma ANP or ANPmRNA and right atrial ANP concentrations. These data suggest that right atrial ANP synthesis is regulated by cardiac filling pressures and possibly by plasma ANP levels, independent from corresponding ANP tissue concentrations.

Aged↗

A possible linkage of atrial natriuretic peptide to the immune system.

Recent work has suggested the existence of atrial natriuretic peptide (ANP)-like material in lymphoid follicles of the guinea pig intestine. To follow the hypothesis of an association of ANP with the immune system, we now report that the rat thymus, a primary lymphoid organ, is a site of ANP synthesis. This is based on the following experimental evidence: firstly, the material detected corresponds chromatographically with the precursor of ANP. Secondly, the existence of mRNA for ANP in the gland suggests synthesis of the peptide in the gland. Thirdly, immunohistochemical studies locate ANP-like material in cortical thymocytes, predominantly in the subcapsular areas of the thymus. Both ANP-like material and mRNA were present to a larger extent in very young rats. The results communicated here support the notion of a link of ANP with the immune system.

Aging↗

[Bilateral adrenal pheochromocytoma. Diagnosis and follow-up using the clonidine test and measurement of plasma neuropeptide Y concentration].

The role of the clonidine suppression test and determination of the plasma concentration of noradrenaline and of neuropeptide Y (NPY) for the diagnosis and monitoring of bilateral pheochromocytoma was studied in a ten year old girl. Prior to tumor removal plasma concentration of noradrenaline (25.9 nmol/l) and NPY (14 pmol/l) were markedly elevated. Inhibition of central sympathetic activity by clonidine (150 micrograms orally) did not lower the plasma concentration of noradrenaline (70.4 nmol/l) and NPY (52.6 pmol/l). However in an adolescent boy with renal hypertension plasma concentration of noradrenaline and NPY fell following clonidine application (noradrenaline from 1.9 to 1.3 nmol/l, NPY from 3.6 to 2.4 pmol/l). After complete removal of the pheochromocytoma noradrenaline and NPY fell back to normal.

Adrenal Gland Neoplasms↗

Hormonal changes after parabolic flight: implications on the development of motion sickness.

Twenty-two different humoral parameters including stress-, gastrointestinal- and volume-regulating hormones were measured before and within 45 min after parabolic flight maneuvers of twenty healthy adult subjects. We compared hormonal data of motion sickness-affected participants with those unaffected. Changes in cortisol and vasoactive intestinal peptide plasma levels were significantly different (p less than 0.002 and p less than 0.004) between the two groups with increasing plasma levels of both hormones during motion sickness but decreasing levels within the control group. Growth hormone and prolactin plasma levels increased by 400% and 115% within the motion sickness-affected group and to a smaller degree (120% and 40% increases, respectively) within the control group, while ACTH levels were almost unchanged within both groups. Pancreatic polypeptide and gastrin plasma levels as well as plasma levels of insulin and C-peptide were significantly decreased within both groups after the parabolic flight. Plasma renin, aldosterone, atrial natriuretic peptide and cyclic GMP levels were unchanged within the control group. Within the motion sickness-affected group, plasma renin and aldosterone levels were decreased and atrial natriuretic peptide levels increased after the flight. Humoral parameters of the thyroid gland were neither changed within the groups nor different between the groups. The present data confirm previous results that increases in plasma levels of certain stress hormones participate in motion sickness. Furthermore, increases in vasoactive intestinal peptide levels participate in motion sickness. These increases could explain some of the gastrointestinal symptoms in motion sickness and might serve as markers for a discrimination between regular stress and motion sickness.

Female↗