ularitide and Body-Weight

Effects of hypobaric hypoxemia on endocrine and renal parameters of body fluid homeostasis were investigated in eight normal men during a sojourn of 8 days at an altitude of 4,559 m. Endocrine and renal responses to an osmotic stimulus (5% hypertonic saline, 3.6 ml/kg over 1 h) were investigated at sea level and on day 6 at altitude. Several days of hypobaric hypoxemia reduced body weight (-2.1 +/- 0.4 kg), increased plasma osmolality (+5.3 +/- 1.4 mosmol/kgH(2)O), elevated blood pressure (+12 +/- 1 mmHg), reduced creatinine clearance (122 +/- 6 to 96 +/- 10 ml/min), inhibited the renin system (19.5 +/- 2.0 to 10.9 +/- 0.9 mU/l) and plasma vasopressin (1.14 +/- 0.16 to 0.38 +/- 0.06 pg/ml), and doubled circulating levels of norepinephrine (103 +/- 16 to 191 +/- 35 pg/ml) and endothelin-1 (3.0 +/- 0.2 to 6.3 +/- 0.6 pg/ml), whereas urodilatin excretion rate decreased from day 2 (all changes P < 0.05 compared with sea level). Plasma arginine vasopressin response and the antidiuretic response to hypertonic saline loading were unchanged, but the natriuretic response was attenuated. In conclusion, chronic hypobaric hypoxemia 1) elevates the set point of plasma osmolality-to-plasma vasopressin relationship, possibly because of concurrent hypertension, thereby causing hypovolemia and hyperosmolality, and 2) blunts the natriuretic response to hypertonic volume expansion, possibly because of elevated circulating levels of norepinephrine and endothelin, reduced urodilatin synthesis, or attenuated inhibition of the renin system.

Topics: Adaptation, Physiological; Adult; Aldosterone; Altitude; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Creatinine; Endothelin-1; Epinephrine; Heart Rate; Humans; Hypertonic Solutions; Hypoxia; Infusions, Intravenous; Kidney; Kidney Function Tests; Male; Norepinephrine; Osmolar Concentration; Peptide Fragments; Renin; Sodium Chloride

The objective of this investigation was to study both the pharmacokinetics and renal pharmacodynamic properties of intravenously infused urodilatin in human beings.. Twelve healthy subjects received a short-term infusion (90 minutes) of urodilatin and placebo with a graded infusion rate (from 7.5 to 15 to 30 ng.kg body weight-1.min-1) in a randomized, double-blind, crossover study design. The renal parameters were evaluated by clearance technique with the use of 51Cr-ethylenediaminetetraacetic acid, 125I-hippuran, and lithium. Urodilatin concentrations were determined by a radioimmunoassay with a urodilatin-specific antibody.. Kinetics were characterized by a high apparent volume of distribution (43.7 +/- 11.2 L), a high total body clearance (5383 +/- 581 ml/min), and a short plasma half-life (5.57 +/- 0.8 minutes). The maximal plasma urodilatin level was 177.2 +/- 25.8 pmol/L. Less than 1% of total infused urodilatin was recovered in urine. Urodilatin significantly increased glomerular filtration rate (urodilatin, 7.0%, versus placebo, -1.9%; p < 0.05), reduced effective renal plasma flow (urodilatin, -17%, versus placebo, -3%; p < 0.01), increased fractional excretion of sodium (urodilatin, 137%, versus placebo, 27%; p < 0.05), and increased urine flow rate (urodilatin, 46%, versus placebo, -15%; p < 0.01). Fractional excretion of lithium did not change. Mean blood pressure decreased and vasoactive hormone levels remained unchanged or increased.. The natriuretic and diuretic effects of urodilatin closely followed the profile of urodilatin concentration in plasma. A major part of the synthetic urodilatin was removed from circulation by a route other than filtration through the glomeruli.

Topics: Adult; Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cross-Over Studies; Cyclic GMP; Diuretics; Double-Blind Method; Heart Rate; Hematocrit; Humans; Infusions, Intravenous; Kidney; Lithium; Male; Metabolic Clearance Rate; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Renin; Sodium

Urodilatin (URO) is a member of the natriuretic family, cleaved by the kidney, which acts as a paracrine hormone in the regulation of natriuresis and diuresis. In newborn infants the excretion of urodilatin and its biological effects have not been explored.. We measured urinary URO excretion, by direct RIA (radioimmunoassay), as well as its correlation to neonatal body weight loss, and sodium homeostasis in 30 full-term newborn infants on the 4th day of life.. The URO excretion, estimated as URO:creatinine ratio, was significantly correlated to sodium excretion.. These data show that in full-term newborn infants the mechanisms that control synthesis, excretion and signal transduction of URO are developed and that URO contributes to natriuresis regulation.

Topics: Apgar Score; Atrial Natriuretic Factor; Body Weight; Creatinine; Homeostasis; Humans; Infant, Newborn; Natriuresis; Peptide Fragments; Sodium; Weight Loss

The purpose of this study was to characterize the hormonal responses to a restraining system in four adult male rhesus monkeys (Macaca mulatta) in preparation for a spaceflight project. After the monkeys were accustomed to food and water (Phase I), blood-volume-regulating hormones were measured during three phases: 10 days in a metabolic cage (Phase II), 16 days sitting in a restrained position in a specially designed metabolism chair (Phase III) and 10 days in metabolic cage (Phase IV). An increase of active renin (30%) and vasopressin (25%) was observed at the end of Phase III. A decrease of atrial natriuretic peptide (ANP), urodilatin, and sodium excretion occurred during the first days of Phase III. Catecholamines were unchanged. A dramatic increase (tenfold) in urinary excretion of growth hormone occurred during all of Phase III and at the beginning of Phase IV. These findings are similar to those found in man during isolation inactivity and during confinement stress.

Topics: Aldosterone; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Body Weight; Catecholamines; Creatinine; Growth Hormone; Heart Rate; Hormones; Humans; Hydrocortisone; Macaca mulatta; Male; Peptide Fragments; Renin; Restraint, Physical; Social Isolation; Sodium; Stress, Psychological; Time Factors; Urea; Vasopressins