Wt Iv Research Articles

2-Adrenergic Receptor-Mediated Regulation of Growth Hormone Secretion in Meal-Fed Holstein Steers

Effects of activation or blockade of alpha 2-adrenergic receptors on serum growth hormone concentrations were studied in Holstein steers (115 +/- 4 days of age; 112 +/- 4 kg body wt). A pelleted diet was available ad libitum for 2 hr each day. Serum growth hormone concentrations were greater for 80 min immediately before feeding compared with 80 min immediately after removal of feed. Relative to saline-injected controls, activation of alpha 2-adrenergic receptors with clonidine (2 micrograms/kg body wt iv) before feeding rapidly increased serum growth hormone concentrations, but clonidine had no effect when administered after feeding. Compared with vehicle-injected controls, blockade of alpha 2-adrenergic receptors with either idazoxan (20 mg/kg body wt sc) or yohimbine (5 mg/kg body wt sc) decreased serum growth hormone concentrations before as well as after feeding. Feeding abolished the stimulatory alpha 2-adrenergic receptor-mediated increase in growth hormone secretion. Our data support the hypothesis that alpha 2-adrenergic receptor stimulation is an essential event mediating pulsatility of growth hormone secretion before feeding and is required to maintain basal concentrations after feeding.

NPY is not a primary mediator of the acute thyroid blood flow response to sympathetic nerve stimulation

It has been suggested that thyroid blood flow is regulated by both sympathetic and parasympathetic nerves. The purpose of our experiments was to study the role of neuropeptide Y (NPY) in the sympathetic neural control of thyroid blood flow. Sympathetic nerve fibers to the thyroid contain both norepinephrine (NE) and NPY. Therefore, NE (15 nmol iv bolus) and NPY (12 or 1.7 nmol/kg body wt iv infusion; 4 min) were administered to anesthetized male rats (250-300 g) either alone or together, with or without an alpha-adrenergic receptor blocker (phentolamine; 10 mg/kg body wt iv bolus). Experiments were also performed in which the cervical sympathetic trunks were stimulated (30 Hz, 10 V; 0.5 ms; 2 min) with or without phentolamine. Thyroid blood flow was monitored continuously by laser-Doppler blood flowmetry. Results are expressed as thyroid vascular conductance (TVC). NE or NPY at both doses decreased TVC relative to that in control saline-infused rats (P < 0.05). No potentiation of the NE effect by NPY was observed when the first dose of NE was injected 2 min after a high or low dose of NPY. However, the effect of a second dose of NE, injected 15 min after the end of the low dose of NPY, was prolonged compared with the effect of a second dose of NE in saline-infused rats. Phentolamine blocked the effect of NE but not that of NPY. Stimulation of the cervical sympathetic trunks decreased TVC (P < 0.01 vs. sham), and this effect was completely blocked by phentolamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan, but not streptozotocin, increases blood perfusion of pancreatic islets in rats.

It has recently been shown that selective B-cell toxins alloxan and streptozotocin (STZ) possess marked effects also on the vascular system. To evaluate to what extent changes in blood perfusion of islets induced by alloxan or STZ could be of importance for diabetogenic action of these compounds, we first investigated acute effects of alloxan (75 mg/kg body wt iv) and STZ (40 mg/kg body wt iv) on both whole pancreatic blood flow (PBF) and islet blood flow (IBF) in adult rats. Alloxan caused a marked increase in IBF, which was most pronounced 3 min after administration and remained for 30 min. PBF, however, was decreased 3 min after alloxan administration but was similar to that of control animals from 10 min and onward. These two opposite effects on IBF and PBF caused the fraction of whole PBF diverted through islets to increase from approximately 10 to 50%. Pretreatment with glucose (2 g/kg body wt iv), indomethacin (3.5 mg/kg body wt iv), dimethyl sulfoxide (10 ml/kg body wt ip of a 33% solution), superoxide dismutase (SOD, 1,000 kU/kg body wt iv), NG-methyl-L-arginine (30 mg/kg body wt iv), theophylline (7 mg/kg body wt iv), or terbutaline (1 mg/kg body wt iv) failed to affect stimulation of IBF by alloxan observed at 3 min. SOD was found to exert a marked stimulation of IBF both when given alone and together with alloxan. Alloxan increased IBF and decreased PBF also in a syngeneic pancreaticoduodenal graft in rats but did not affect flow distribution in a perfused pancreas-duodenum preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Phasic and 24-h blood pressure control by endothelium-derived relaxing factor in conscious dogs.

The effects of blocking endothelium-derived relaxing factor (EDRF) on 24-h blood pressure and heart rate (HR) were examined in six conscious freely moving foxhounds. The hypothesis tested was that shear stress-dependent EDRF release acts as a physiological blood pressure buffer. Telemetry recordings were obtained before and after the administration of the false substrate for EDRF synthesis NG-nitro-L-arginine (L-NNA, 16.5 +/- 2 mg/kg body wt iv). In response to L-NNA, mean arterial blood pressure (MAP) increased from 116 +/- 5 to 134 +/- 5 mmHg (P less than 0.01) and HR decreased from 97 +/- 6 to 68 +/- 3 beats/min over the entire 24-h period (P less than 0.01). The overall variability of MAP (as indicated by SD of frequency distribution) increased modestly from 9.5 +/- 0.4 to 11.7 +/- 1.1 mmHg (P less than 0.05). A sequential spectral analysis of blood pressure showed a 2.1-fold increase of power in the frequency range of 0.01-0.5 Hz (P less than 0.05) after L-NNA was given. In conclusion, blockade of EDRF led to a sustained hypertension throughout the whole 24-h recordings. Furthermore, EDRF acted as a physiological blood pressure buffer in the frequency range below 0.5 Hz.

Effects of alpha 1-adrenergic blockade on intrarenal hemodynamics in heart failure rats.

To investigate intrarenal hemodynamics and effects of alpha 1-adrenergic blockade on glomerular functions in congestive heart failure (CHF), micropuncture studies were performed before and after intravenous injection of terazosin (1 microgram/100 g body wt iv) in eight myocardial infarction (MI) and in nine sham-operated rats after intraperitoneal injection of Inactin (70 mg/kg). CHF was characterized by elevated left ventricular end-diastolic pressure and increased total heart weight. In CHF rats, single nephron glomerular filtration rate (SNGFR), single nephron plasma flow (SNPF), and ultrafiltration coefficient (Kf) were decreased compared with sham-operated rats (SNGFR, 21.9 +/- 1.6 vs. 39.2 +/- 2.9 nl.min-1.g-1, P less than 0.01; SNPF, 66.6 +/- 6.1 vs. 133.8 +/- 10.5 nl.min-1.g-1, P less than 0.01; Kf, 0.019 +/- 0.001 vs. 0.041 +/- 0.004 nl.s-1.mmHg-1.g-1, P less than 0.01). Single nephron filtration fraction (SNFF), glomerular pressure (Pg), and efferent arteriolar resistance (Re) were higher in the CHF-MI rats than in the sham-operated rats (SNFF, 33.4 +/- 1.3 vs. 27.7 +/- 1.0, P less than 0.05; Pg, 60.2 +/- 1.6 vs. 53.3 +/- 0.8 mmHg, P less than 0.01; Re, 3.92 +/- 0.66 vs. 1.62 +/- 0.15 x 10(10) dyn.s.cm-5.g, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intravenous injection of IL-1 beta on PGE2 levels in several brain areas as determined by microdialysis.

Using perfusion microdialysis, the effect of intravenous injection of recombinant human interleukin-1 beta (IL-1 beta) on prostaglandin E2 (PGE2) release into the interstitial fluid of the organum vasculosum laminae terminalis (OVLT), medial preoptic area (MPOA), paraventricular nucleus (PVN), dorsal hippocampus (HPC), and cerebrospinal fluid (CSF) of the lateral ventricle (LV) was examined. Artificial CSF was perfused through the dialysis probe and collected at 20-min intervals before and after IL-1 beta (1 microgram/100 g body wt iv). The results showed that 1) IL-1 beta induced a significant increase in PGE2 levels in the OVLT and the medial part of the MPOA in the first 20 min, which is more rapid and to a greater extent than that in PVN, HPC, and LV; 2) inclusion of indomethacin in the perfusate abolished the IL-1 beta-induced PGE2 response in the OVLT, but a suppressive effect in the PVN was insignificant. These results suggest that OVLT may be a gate for the entry of blood-borne IL-1 beta into the brain and a site where the initial biochemical response to IL-1 beta occurs.

Migration and proliferation of cultured neural crest cells in W mutant neural crest chimeras

Chimeric mice, generated by aggregating preimplantation embryos, have been instrumental in the study of the development of coat color patterns in mammals. This approach, however, does not allow for direct experimental manipulation of the neural crest cells, which are the precursors of melanoblasts. We have devised a system that allows assessment of the developmental potential and migration of neural crest cells in vivo following their experimental manipulation in vitro. Cultured C57Bl/6 neural crest cells were microinjected in utero into neurulating Balb/c or W embryos and shown to contribute efficiently to pigmentation in the host animal. The resulting neural crest chimeras showed, however, different coat pigmentation patterns depending on the genotype of the host embryo. Whereas Balb/c neural crest chimeras showed very limited donor cell pigment contribution, restricted largely to the head, W mutant chimeras displayed extensive pigmentation throughout, often exceeding 50% of the coat. In contrast to Balb/c chimeras, where the donor melanoblasts appeared to have migrated primarily in the characteristic dorsoventral direction, in W mutants the injected cells appeared to migrate in the longitudinal as well as the dorsoventral direction, as if the cells were spreading through an empty space. This is consistent with the absence of a functional endogenous melanoblast population in W mutants, in contrast to Balb/c mice, which contain a full complement of melanocytes. Our results suggest that the W mutation disturbs migration and/or proliferation of endogenous melanoblasts. In order to obtain information on clonal size and extent of intermingling of donor cells, two genetically marked neural crest cell populations were mixed and coinjected into W embryos. In half of the tricolored chimeras, no co-localization of donor crest cells was observed, while, in the other half, a fine intermingling of donor-derived colors had occurred. These results are consistent with the hypothesis that pigmented areas in the chimeras can be derived from extensive proliferation of a few donor clones, which were able to colonize large territories in the host embryo. We have also analyzed the development of pigmentation in neural crest cultures in vitro, and found that neural tubes explanted from embryos carrying wt or weak W alleles produced pigmented melanocytes while more severe W genotypes were associated with deficient pigment formation in vitro.

Model of the distribution and metabolism of a GnRH superagonist in dogs

The plasma kinetics of [D-Trp6, des-Gly-NH2(10)]gonadotropin-releasing hormone (GnRH) ethylamide was assessed in eight dogs over a period of 8 h after rapid intravenous or subcutaneous injection. Each animal received doses of 0.2, 2, and 20 micrograms/kg body wt iv and 1 and 10 micrograms/kg body wt sc. A two-compartment structure, to which a source compartment was added to represent the subcutaneous route, adequately fits the five kinetics when the apparent volume of distribution follows a plasma concentration-dependent sigmoid function. Despite the nonlinearity, the apparent volume of distribution can be approximated by a constant value of 280 ml/kg body wt for the dynamics corresponding to the three lowest and more physiological doses. The metabolic clearance rate is 4.63 ml.min-1.kg body wt-1. The two exponential components that characterize the two-compartment structure are equal to 0.0348 +/- 0.0053 and 0.00470 +/- 0.00060 min-1, respectively. The agonist injected subcutaneously diffuses to plasma at a fractional rate of 0.0265 +/- 0.0029 min-1. Disposal occurs at a maximal rate of 0.017 and 0.0055 min-1 of the amount of agonist present in the central and peripheral compartments, respectively. The highest fractional exchange rate between compartments reaches 0.01 min-1. As simulated with the model, a continuous infusion of 4.63 ng.min-1.kg body wt-1 leads to a steady state of 1 ng/ml plasma; 90% of that level is reached 7 h after the onset of the subcutaneous input signal. The kinetics of plasma [D-Trp6, des-Gly-NH2(10)]GnRH ethylamide is many times slower than that of the native hormone and of the other GnRH agonists.

Adrenergic blockade prevents endotoxin-induced increases in glucose metabolism.

Combined alpha- and beta-adrenergic blockade was used to investigate the role of catecholamines in endotoxin-induced elevations in glucose kinetics. Glucose kinetics were measured before and for 4 h after the injection of endotoxin [100 micrograms/100 g body wt iv, 30% lethal dose (LD30) at 24 h]. Adrenergic blockade was achieved by the bolus injection of phentolamine and propranolol followed by their continuous infusion. Endotoxin-treated rats exhibited a transient hyperglycemia and sustained (greater than 4 h) increase in plasma lactate concentration, as well as elevated rates of glucose appearance (Ra, 83%), disappearance (Rd, 58%), recycling (160%), and metabolic clearance (23%). Adrenergic blockade prevented endotoxin-induced increases in plasma glucose concentration, Ra, Rd, and recycling but not glucose clearance. The increase in plasma lactate concentration was blunted by 35%. After 2 h, endotoxic animals infused with adrenergic antagonists developed hypoglycemia, which may have resulted from an increased plasma insulin concentration. The attenuation of elevated glucose turnover by adrenergic blockade in the endotoxin-treated animals was not due to a reduction in plasma glucagon level or differences in plasma insulin concentration. Administration of the alpha- or beta-adrenergic antagonists separately blunted but did not prevent endotoxin-induced changes in glucose kinetics, and therefore the efficacy of the adrenergic blockade could not be assigned to a single receptor class. These results indicate that catecholamines are important contributory factors to many of the early alterations in carbohydrate metabolism observed during endotoxemia.

Forward diastolic flow in pulmonary artery induced by right atrial contraction of pig hearts.

To study whether right atrial contraction can forward blood into the pulmonary artery during diastole, blood volume was expanded in anesthetized open-chest pigs until mean right atrial pressure was 13-20 mmHg (range). In the control situation, blood flow in the pulmonary artery was only observed during ventricular systole. Forward diastolic pulmonary artery flow, coinciding with right atrial contraction, was observed when diastolic pulmonary artery pressure was reduced during selectively increased left-side contractility, during bradycardia after propranolol injection (0.5 mg/kg body wt iv), and during the prolonged diastolic interval after spontaneously occurring atrial extrasystoles. The prolongation of the diastolic interval in all three series caused the diastolic pulmonary artery pressure to decline and the filling of the right atrium to increase, thus further stimulating the right atrial Frank-Starling mechanism. The diastolic blood flow in the pulmonary artery constituted 11% of the stroke volume during increased left-side inotropic stimulation, 8% during bradycardia, and 6% in beats preceded by a prolonged diastolic interval. Thus, in the normal heart, blood can be ejected into the pulmonary artery during right atrial contraction.

Indirect evidence of glomerular/tubular mixed-type postexercise proteinuria in healthy humans.

Hypothetical mechanisms have been postulated to explain the presence of proteins in urine after severe exercise. Recently, it has been shown that several amino acids inhibit tubular protein reabsorption. Seven healthy men, hyperhydrated, were studied during a 2-min bicycle exercise at supramaximal load. The subjects were tested without or with lysine perfusion (0.4 g/kg body wt iv). In both testing conditions, blood lactate increased to 13.8 mmol/l. Total protein urinary excretion increased to 1.10 and 1.67 mg/min, without and with lysine perfusion, compared with 79 micrograms/min at rest. In the meantime, albumin excretion increased 48- and 74-fold, respectively, while beta 2-microglobulin excretion increased 97- and 1,043-fold compared with basal values. The renal clearance of albumin increased to 8.4 microliters/min without lysine and to 12.0 microliters/min with lysine perfusion (rest 0.18). beta 2-Microglobulin clearance increased to 10.0 and 39.3 ml/min, respectively (rest 0.05). These data clearly demonstrate that postexercise proteinuria is of mixed type after exhaustive short-term exertion. Both increased glomerular permeability and partial tubular reabsorption inhibition to proteins appear to be involved.

Early pulmonary endothelial enzyme dysfunction after phorbol ester in conscious rabbits.

We investigated changes in angiotensin converting-enzyme (ACE) activity before and at 5, 15, 60, and 240 min after 20 micrograms phorbol myristate acetate/kg body wt iv in conscious rabbits. ACE activity was estimated in vivo from the single-pass transpulmonary metabolism of the synthetic substrate [3H]benzoyl-Phe-Ala-Pro [( 3H]BPAP) under first-order reaction conditions. Within 5 min after PMA administration, all animals developed profound granulocytopenia (15% of control) and moderate thrombocytopenia (57% of control), both lasting for the duration of the experiment. Concomitantly, there was a significant decrease in the transpulmonary metabolism of [3H]BPAP and the calculated apparent first-order reaction constant Amax/Km of ACE for [3H]BPAP. No histological evidence of lung injury was observed at these times. Since a concomitant fall in the permeability surface area product for urea was also observed, we considered that the apparent decline in ACE activity might have resulted from a reduction in perfused endothelial surface area. To resolve this, we studied the effect of PMA on the Km (a measure of enzyme affinity for its substrate) and Amax (a derivative of Vmax that is dependent upon total enzyme present and thus capillary surface area) of ACE and 5'-nucleotidase for [3H]BPAP and [14C]AMP, respectively. A significant increase in Km for both enzymes was observed at 1 h after PMA, whereas Amax was unaffected, suggesting that low-dose PMA may indeed produce endothelial cell enzyme dysfunction independent of its effect on capillary surface area. These results provide evidence of pulmonary capillary functional injury before or in the absence of structural endothelial damage.

IP3-dependent Ca2+ release in permeabilized hepatocytes of endotoxemic and septic rats.

Inositol trisphosphate-dependent Ca2+ release was measured in saponin-permeabilized hepatocytes isolated from acutely (2 mg/100 g body wt iv) or chronically (0.1 mg X 100 g body wt-1 X 24 h-1 for 30 h) endotoxin-treated (ET, Escherichia coli) rats or from animals rendered septic by cecal ligation and puncture. A decrease of this parameter was observed in acutely ET-treated rats (52%, P less than 0.01) and after 30 h of continuous ET infusion (33%, P less than 0.01). Sepsis was associated with an elevated Ca2+ release (34%, P less than 0.01) as compared with the sham-operated animals. We conclude that during endotoxicosis and sepsis alterations of intracellular Ca homeostasis take place, reaching sites beyond the level of the plasma membrane. Such alterations could account in part for metabolic and functional changes associated with these pathologic states. In addition, ET treatment provides the first known intervention resulting in the modulation of inositol trisphosphate-dependent Ca2+ release.

Renal degradation and distribution between urinary and venous output of prostaglandins E2 and I2.

To examine renal degradation and distribution between urine and renal venous blood, prostaglandins E2 and I2 (PGE2 and PGI2), and a metabolite of PGI2, 6-keto-PGF1 alpha, were infused into the suprarenal aorta of anaesthetized dogs after blocking prostaglandin synthesis by indomethacin, 10 mg kg-1 body wt iv. During one passage through the kidney 80% of PGE2 and only 25% of PGI2 and 6-keto-PGF1 alpha were metabolized. Prostaglandin degradation and arterial input were proportional (r greater than 0.90). To stimulate the intrarenal prostaglandin synthesis in unblocked kidneys, arachidonic acid was infused at rates ranging from 24 to 160 micrograms min-1 kg-1 body wt. During arachidonic acid and PGE2 infusion the urinary excretion of PGE2 was about 20% of the renal venous output over a wide range of infusion rates. During arachidonic acid and PGI2 infusion urinary excretion of 6-keto-PGF1 alpha was about 10% of total renal output, but failed to increase further when total renal output exceeded 70 pmol min-1. Further increase in output occurred only in the renal vein. In contrast, during 6-keto-PGF1 alpha infusion the urinary excretion and the renal venous output of this metabolite were related as 1:2 over a wide range of infusion rates. Thus, PGI2 is much less degraded by renal tissue than PGE2, and the distribution patterns differ. Similar distributions between urine and renal venous blood during aortic infusion and stimulated intrarenal synthesis suggest a pre-glomerular vascular origin of both prostaglandins.

Beta-endorphin-induced hyperglycemia in rabbits: effects of a glucose or arginine challenge.

The effects of beta-endorphin on glucose, insulin, and glucagon levels were studied in normal fasted adult male rabbits. An intravenous bolus of glucose (0.7 g/kg body wt) produced a hyperglycemic state (peak plasma glucose 306 +/- 22 mg/dl; means +/- SE) that lasted approximately 90 min. beta-Endorphin (31 micrograms/g body wt; iv) administered immediately prior to the glucose challenge resulted in plasma glucose levels that were significantly higher from 10 to 90 min after the glucose challenge (P less than 0.001-0.05). From 10 to 30 min, plasma insulin levels were significantly lower in the beta-endorphin group (P less than 0.001-0.05), peaking at one-half the control group levels. Glucagon levels were unchanged by the glucose bolus in either the control or beta-endorphin-treated group (means +/- SE = 102.8 +/- 4 pg/ml). In another experiment, a 30-min infusion of L-arginine (13 mg-1 X kg body wt-1 X min iv) in normal fasted rabbits produced a rapid (10 min) increase in plasma insulin and glucagon and a return to base-line levels 60 min after withdrawing the arginine stimulus. Plasma glucose levels were not altered by arginine (mean +/- SE = 94.5 +/- 1 mg/dl). Administration of beta-endorphin (31 micrograms/kg body wt iv) at the start of the arginine infusion resulted in a rapid (10 min) and long-lasting (up to 60 min) hyperglycemic effect associated with a significant decrease in insulin levels (10-20 min; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of streptozocin-induced diabetes and weight-matched pair feeding on tumor growth and survival in fischer rats

Sixty-one 150- to 180-g Fischer rats were assigned to one of four experimental groups: nondiabetic, tumor bearer (ND-TB, n = 15); diabetic, non-tumor bearer (D-NTB, n = 19); diabetic, tumor bearer (D-TB, n = 16); or nondiabetic, weight-matched control, tumor bearer (WM-TB, n = 11). The WM group was housed in metabolic cages and fed H 2O ad libitum and rat chow to achieve appropriate carcass weight (comparable to D-NTB). Diabetes was induced with a single dose of streptozocin (STZ) 40 mg/kg body wt iv, 10 days prior to tumor inoculation. Viable methylcholanthrene-induced sarcoma cells (1 × 10 6) were injected into the right flank on Day 0. Body weight and tumor volume were assessed every 3 days. On the day of death, the animal and excised tumor were weighed. Dividing the growth curves versus time into two phases based on tumor volumes 0–20 and 20–60 cm 3 defined a significant early growth (0–20 cm 3) delay of 5 days in the D-TB and WM groups vs the ND-TB group. The growth rate from 20–60 was not different in any group. Tumor growth retardation seen in STZ-induced diabetic animals can be mimicked and exceeded in a pair-fed, weight-matched control group. Diabetic and starved animals have smaller tumors and live longer than ad lib fed, nondiabetic animals. The delay in tumor growth is a reflection of the retardation in the early (0–20 cm 3) growth rate.

Inhibition of transcellular NaCl reabsorption in dog kidneys during hypercalcemia.

Reduced concentrating and diluting capacity of the kidney in acute and chronic hypercalcemia may partly be due to inhibition of transcellular sodium reabsorption (RNa) in the thick ascending limb of Henle's loop. To examine this hypothesis, local heat production and RNa were measured during normo- and hypercalcemia at comparable glomerular filtration rate (GFR) in volume expanded, anesthetized dogs. Changes in proximal RNa which might occur during CaCl2 infusion, were minimized by infusing acetazolamide (75 mg/kg body wt iv). When ultrafiltrable calcium was increased from 1.12 +/- 0.09 to 2.95 +/- 0.10 mmol/l, cortical heat production was unchanged, whereas outer medullary heat production fell by 32 +/- 4%. RNa was reduced by 32 +/- 6%. Bicarbonate reabsorption did not change but calcium reabsorption and potassium excretion increased significantly. The potassium content of cortex and outer medulla increased during hypercalcemia, whereas ouabain, an inhibitor of Na+, K+-ATPase reduces the potassium content. We conclude that hypercalcemia does not inhibit transcellular RNa in the diluting segment by a direct effect on the Na+, K+-ATPase or the mitochondria, but by interfering with the coupled NaCl transport across the luminal cell membrane.

Further in vivo evidence for antagonist-to-antidiuretic action of arginine vasopressin.

The effect of a new arginine vasopressin (AVP) analogue, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-ethyltyrosine, 4-valine]AVP or d(CH2)5Tyr(Et)VAVP, was examined on exogenous and endogenous AVP in the conscious rat. An intravenous injection of 8 micrograms/kg body wt of the AVP analogue completely blocked the antidiuretic effect of exogenous AVP (4 ng/kg body wt iv). Similarly, 8 micrograms/kg of the AVP analogue totally abolished the antidiuretic effect of infused AVP (0.1 mU X kg-1 X min-1) in the homozygous Brattleboro rats with central diabetes insipidus. The antagonism of this antidiuretic effect of exogenous AVP occurred in the absence of changes in urinary solute excretion, glomerular filtration rate (GFR), and mean arterial pressure. Intraperitoneal administration of the AVP analogue (30 micrograms/kg body wt) decreased the mean urinary osmolality in rats after 24 h of fluid deprivation from 3,098 +/- 140 to 797 +/- 155 mosmol/kg H2O (P less than 0.001). The duration of the antagonism of endogenous AVP was approximately 4.5 h. The antagonism of AVP was not dependent on the vascular properties of AVP, since the AVP analogue also blocked the antidiuretic effect of exogenous 1-deamino-8-D-AVP (DDAVP), an AVP analogue with negligible vascular properties. These in vivo results therefore indicate that d(CH2)5Tyr(Et)VAVP is a specific antagonist of the hydrosmotic effect of exogenous and endogenous AVP. In contrast to some previous analogues, this effect of the AVP analogue occurred in the absence of any known diuretic factors including an increase in GFR, solute excretion, and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of parathion on renal water and electrolyte excretion in the dog

The effect of a single low dose of parathion on renal water and electrolyte excretion was studied in anesthetized mongrel dogs. Sodium excretion significantly increased 20 min after iv administration of 1.5 μg parathion/kg body wt, while urine output slightly increased and potassium excretion significantly decreased. No change was observed in glomerular filtration rate, renal plasma flow, filtration fraction, and plasma sodium concentration. Respiratory frequency, heart rate, and arterial blood pressure remained unchanged throughout the experiments. With the doses used, no inhibition of acetylcholinesterase in red blood cells or renal tissues was found. The administration of a single dose of 1 μg atropine sulfate/kg body wt iv had no effect in all the parameters measured but was able to completely block the natriuretic effect of parathion when given ten minutes prior to parathion. Since the dose used showed no inhibitory effect on acetylcholinesterase, it is unlikely that the natriuretic effect of parathion could be due to changes in enzyme activity but rather to conformational changes in tubular membranes altering sodium reabsorption.

Effect of hypothalamic surgery on prolactin release induced by 5-hydroxytryptophan (5-HTP) in rats.

Intravenous injections of varying doses of 5-HTP (1, 3 and 5 mg/100 g body wt), a precursor of serotonin, caused a significant and dose-related increase in plasma prolactin concentrations in urethane-anesthetized rats. Increases in plasma prolactin concentrations caused by 5-HTP (1 mg/100 g body wt iv) were abolished by the concomitant administration of L-DOPA (2 mg/100 g body wt iv). Plasma prolactin levels were also significantly elevated following the injection of 5-HTP in rats with complete hypothalamic deafferentation, whereas 5-HTP had no significant effect on plasma prolactin levels in rats with extensive hypothalamic ablation. These results suggest that 5-HTP causes prolactin secretion by stimulating the serotoninergic mechanism in the hypothalamus.