atrial-natriuretic-factor and Hypercapnia

Disturbances in hormonal systems involved in sodium and water homeostasis are common during respiratory insufficiency. To investigate the role of hypercapnia, we designed a study to examine the hormonal response to acute hypercapnia induced at constant cardiac filling pressures and without hypoxemia. Seven sedated patients with COPD receiving mechanical ventilation were studied during five successive periods. Hemodynamics, arterial blood gases, and plasma hormone levels (atrial natriuretic peptide, renin, angiotensin II, aldosterone, vasopressin) were measured three times during 60 min of acute hypercapnia (52 +/- 5 mm Hg) and at control periods, before (36 +/- 4 mm Hg) and after (42 +/- 3 mm Hg) acute hypercapnia. During acute hypercapnia, mean pulmonary arterial pressure and cardiac output were increased without variation of other measured cardiorespiratory data and hormonal levels when compared with control values. After acute hypercapnia, cardiorespiratory variables returned to control values without variations of hormonal levels. Our results show that moderate acute hypercapnia does not significantly influence the hormonal levels when cardiac filling pressures and sympathetic tone remain stable. We suggest that changes in those plasma hormones involved in salt and water homeostasis during acute hypercapnia are secondary to hemodynamic changes induced by acute respiratory failure and not to acute hypercapnia per se.

Topics: Aged; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Hemodynamics; Homeostasis; Humans; Hypercapnia; Lung Diseases, Obstructive; Male; Middle Aged; Renin; Respiration, Artificial; Respiratory Dead Space; Vasopressins

The combination of long-term hypercapnia and hypoxia decreases pulmonary vascular remodeling and attenuation of right ventricular (RV) hypertrophy. However, there is limited information in the literature regarding the first stages of acclimatization to hypercapnia/hypoxia. The purpose of this study was to investigate the effect of four-day hypoxia (10% O2) and hypoxia/hypercapnia (10% O2 + 4.4% CO2) on the protein composition of rat myocardium. Expression of the cardiac collagen types and activities of matrix metalloproteinases (MMPs) and of their tissue inhibitor TIMP-1 were followed. The four-day hypoxia changed protein composition of the right ventricle only in the hypercapnic condition; remodeling was observed in the extracellular matrix (ECM) compartments. While the concentrations of pepsin-soluble collagenous proteins in the RV were elevated, the concentrations of pepsin-insoluble proteins were decreased. Furthermore, the four-day hypoxia/hypercapnia increased the synthesis of cardiac collagen due to newly synthesized forms; the amount of cross-linked particles was not affected. This type of hypoxia increased cardiac collagen type III mRNA, while cardiac collagen type I mRNA was decreased. MMP-2 activity was detected on the zymographic gel through appearance of two bands; no differences were observed in either group. mRNA levels for MMP-2 in the RV were significantly lower in both the hypoxic and hypoxic/hypercapnic animals. mRNA levels for TIMP-1 were reduced in the RV of both the hypoxic and hypoxic/hypercapnic animals. Hypoxia with hypercapnia increased the level of mRNA (6.5 times) for the atrial natriuretic peptide (ANP) predominantly in the RV. The role of this peptide in remodeling of cardiac ECM is discussed.

Topics: Animals; Atrial Natriuretic Factor; Collagen Type I; Collagen Type III; Extracellular Matrix Proteins; Gene Expression Profiling; Hypercapnia; Hypoxia; Male; Matrix Metalloproteinases; Myocardium; Peptide Mapping; Rats; Rats, Wistar; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Ventricular Remodeling; Weight Loss

To investigate the effects of hypoxemia, hypercapnia, and cardiovascular hormones (norepinephrine, endothelin-1, and atrial natriuretic factor) on blood pressure during acute respiratory failure.. Patients with chronic obstructive pulmonary disease and acute respiratory failure were divided into four groups of 10 patients each: hypoxemia-normocapnia, hypoxemia-hypercapnia, hypoxemia-hypocapnia, and normoxemia-hypercapnia. Plasma norepinephrine levels were determined by high-performance liquid chromatography with electrochemical detection. Plasma endothelin-1 and atrial natriuretic factor levels were radioimmunoassayed after chromatographic preextraction.. Systolic blood pressure and cardiovascular hormone levels were greater in patients with hypercapnia (whether or not they also had hypoxemia) than in those with normocapnia and hypoxemia. For example, in patients with hypercapnia and normoxemia, the mean (+/- SD) systolic blood pressure was 183+/-31 mm Hg and the mean norepinephrine level was 494+/-107 pg/mL, as compared with 150+/- 6 mm Hg and 243+/-58 pg/mL in those with normocapnia and hypoxemia (both P<0.05). Similar results were seen for endothelin-1 and atrial natriuretic factor levels, and for the comparisons of hypoxemic patients who were hypercapnic with those who were normocapnic.. These results suggest that blood carbon dioxide levels, rather than oxygen levels, are responsible for hypertension during acute respiratory failure, perhaps as a result of enhanced sympatho-adrenergic activity.

Topics: Acute Disease; Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Carbon Dioxide; Endothelin-1; Female; Heart Rate; Humans; Hypercapnia; Hypertension; Hypocapnia; Hypoxia; Lung Diseases, Obstructive; Male; Middle Aged; Norepinephrine; Oxygen; Respiratory Insufficiency; Severity of Illness Index

The aim of this study was to investigate the haemodynamic and endocrinological effects of noninvasive positive pressure ventilation (NIPPV). Eleven patients with oedema and recent hypercapnic and hypoxaemic worsening of a chronic respiratory insufficiency were included. Echocardiography, cardiac radionuclide assessment, blood catecholamines, salt and water handling hormones were measured at admission and discharge (long study (LS)). To discriminate between the action of NIPPV and other treatments, measurements were performed on the fourth day, for 4 h without NIPPV and 4 h with NIPPV (short study (SS)). NIPPV entailed a correction of P(a,CO2) and an increase of P(a,O2) in LS and SS. Oedema disappeared. Body weight decreased (from 85+/-42 to 81+/-40 kg) during LS. Systolic and mean pulmonary arterial pressure decreased in LS and SS. Right ventricular ejection fraction increased in LS. Left ventricular ejection fraction did not change. Cardiac index was normal on admission and then decreased. Natriuretic peptides and catecholamines were increased on admission, whereas plasma renin activity, aldosterone and vasopressin were normal. We suggest that in these patients, oedema can occur independently of renin-angiotensin-aldosterone-vasopressin and with a normal cardiac output. Noninvasive positive pressure ventilation allowed a correction of blood gases, associated with the resolution of oedema, a decrease in pulmonary arterial pressures and an increase in right ventricular ejection fraction.

Topics: Atrial Natriuretic Factor; Body Composition; Case-Control Studies; Edema; Female; Hemodynamics; Hormones; Humans; Hypercapnia; Intermittent Positive-Pressure Ventilation; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pulmonary Wedge Pressure; Respiratory Insufficiency; Ventricular Function, Right; Water-Electrolyte Balance

The effects of somatostatin and atrial natriuretic peptide applied topically to the ventral surface of the medulla (VMS) on tracheal tone and phrenic nerve activity (Phr) were studied in chloralose-anesthetized and paralyzed cats artificially ventilated with 7% CO2 in O2. Surface application of drugs to the chemosensitive areas of the VMS significantly decreased tracheal tension measured by changes in pressure in a balloon placed in a bypassed segment of the trachea (Ptseg). Application of somatostatin (9 cats) caused a mean decrease in Ptseg from 17.3 +/- 1.8 (SE) to 4.3 +/- 1.4 cmH2O (P < 0.01) and a reduction in Phr from 24.9 +/- 3.4 to 10.3 +/- 3.4 units (P < 0.05). Like somatostatin, application of atrial natriuretic peptide to the VMS (5 cats) produced tracheal relaxation (Ptseg decreased from 19.3 +/- 2.6 to 9.9 +/- 1.3 cmH2O, P < 0.01), but in contrast there was an insignificant reduction in Phr (from 18.5 +/- 3.6 to 16.1 +/- 3.8 units, P > 0.05). When parasympathetic activity was abolished by atropine methylnitrate and tracheal tone was restored with 5-hydroxytryptamine, somatostatin and atrial natriuretic peptide applied on the VMS had no effect on tracheal pressure, suggesting that observed changes were not caused by direct action of peptides on tracheal smooth muscle via the bloodstream or by facilitation of inhibitory pathways. Both somatostatin and atrial natriuretic peptide applications were associated with a slight but significant decrease in arterial blood pressure. These data suggest that somatostatin and atrial natriuretic peptide acting on the chemosensitive structure of the VMS may play significant roles in modulating para-sympathetic outflow to airway smooth muscle.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cats; Chemoreceptor Cells; Female; Hypercapnia; Hypoxia; Male; Medulla Oblongata; Muscle Relaxation; Muscle Tonus; Muscle, Smooth; Parasympathetic Nervous System; Phrenic Nerve; Pressure; Somatostatin; Trachea

To investigate the mechanisms of sodium retention in patients with chronic obstructive lung disease (COLD), we examined the renal and hormonal responses to volume expansion with isotonic saline and to infusion of atrial natriuretic factor (ANF) in 10 hypercapnic (PaCO2 52 +/- 2 mm Hg) and 12 normocapnic patients (PaCO2 39 +/- 1 mm Hg). Sodium excreted within 4 h of loading (expressed as % sodium load) was 23.5 +/- 2.5% (p < 0.05) in normocapnic and 8.5 +/- 1.5% (p < 0.001) in hypercapnic patients, compared with 32.5 +/- 3.0% in 11 age-matched control subjects. Sodium excretion and renal blood flow correlated negatively with arterial PCO2 and positively with FEV1. Basal plasma ANF concentrations were 72 +/- 5 pg/ml in controls, 100 +/- 14 pg/ml in normocapnic patients, and 230 +/- 52 pg/ml in hypercapnic patients (p < 0.001). Plasma renin activity and aldosterone did not differ between groups. In response to volume expansion, plasma ANF increased in both normocapnic and controls (with a greater increase in normocapnic patients) but remained unchanged in hypercapnic patients. Exogenous ANF increased glomerular filtration rate, renal plasma flow, natriuresis, and diuresis in both groups of patients. Patients with COLD have depressed renal function that appears unrelated to activation of the renin-angiotensin-aldosterone system. An increased secretory response of ANF to volume expansion may help to maintain volume homeostasis in normocapnic patients, while a blunted secretory response of ANF may contribute to sodium retention in hypercapnic patients.

Topics: Aged; Analysis of Variance; Atrial Natriuretic Factor; Carbon Dioxide; Female; Glomerular Filtration Rate; Humans; Hypercapnia; Infusion Pumps; Least-Squares Analysis; Lung Diseases, Obstructive; Male; Middle Aged; Natriuresis; Renal Plasma Flow

To evaluate the changes in atrial natriuretic polypeptide during acute hypoxemia and acute hypercapnic acidosis, conscious mongrel dogs with controlled sodium intake were evaluated in four protocols: (1) 80 min of acute hypoxemia (PaO2 = 34 +/- 1 mm Hg) followed by 40 min of combined hypoxemia and hypercapnic acidosis (PaO2 = 38 +/- 1 mm Hg, PaCO2 = 60 +/- 3 mm Hg, pH = 7.15 +/- 0.03) (n = 7); (2) 40 min of combined acute hypoxemia and hypercapnic acidosis (PaO2 = 36 +/- 1 mm Hg, PaCO2 = 56 +/- 2 mm Hg, pH = 7.20 +/- 0.03) induced immediately following control measurements (n = 5); (3) 120 min of acute hypercapnic acidosis (PaCO2 = 58 +/- 1 mm Hg, pH = 7.20 +/- 0.01) (n = 5), and (4) 120 min of normoxemia and normocapnia (n = 7). These studies did not observe any association between urinary sodium excretion and circulating atrial natriuretic polypeptide during acute blood gas derangements in conscious dogs. The natriuresis with acute hypoxemia or acute hypercapnic acidosis was unaccompanied by change in plasma atrial natriuretic polypeptide concentrations. Conversely, the rise in circulating atrial natriuretic polypeptide during combined acute hypoxemia and hypercapnic acidosis was not associated with an increase in urinary sodium excretion. These observations do not exclude a role for atrial natriuretic polypeptide in altering sodium excretion during acute blood gas derangements, since the effects of this autacoid on renal sodium excretion may have been offset by other counterregulatory mechanisms of sodium excretion activated during the acute blood gas derangement.

Topics: Acidosis; Animals; Atrial Natriuretic Factor; Dogs; Hypercapnia; Hypoxia; Natriuresis; Nephrectomy

1. The aim of the present study was to assess the effects of hypercapnia or hypoxia on plasma concentrations of atrial natriuretic factor (ANF) in conscious unrestrained dogs. 2. For this purpose, chronically instrumented dogs were exposed in a random order to either room air, or to an atmosphere containing 21% O2/10% CO2/69% N2 to produce hypercapnia, or 10% O2/3% CO2/87% N2 to produce hypoxia without respiratory alkalosis. 3. Plasma concentrations of ANF did not change significantly during hypoxia. 4. In contrast, during hypercapnia, plasma concentrations of ANF increased by more than 100% and returned to baseline at the end of hypercapnia. 5. Hypercapnia, but not hypoxia, induced an increase in left atrial and central venous pressures. 6. We conclude that hypercapnia increases plasma ANF concentration, and that this increase may be secondary to an increase of the left and right atrial pressures. These phenomena may explain the increase in diuresis and natriuresis which has been described during hypercapnia.

Topics: Animals; Atrial Natriuretic Factor; Carbon Dioxide; Dogs; Female; Hematocrit; Hypercapnia; Hypoxia; Male; Oxygen; Partial Pressure; Renin

Topics: Acidosis, Respiratory; Aldosterone; Animals; Atrial Natriuretic Factor; Body Fluids; Body Water; Humans; Hypercapnia; Hypoxia; Kidney; Lung Diseases, Obstructive; Pituitary-Adrenal System; Renin; Sodium Chloride