Changes in atrial natriuretic factor during preload reduction with nitroglycerin in patients with congestive heart failure

Summary. Nine patients with congestive heart failure, New York Heart Association class II-III, were evaluated with right heart catheterization. Plasma atrial natriuretic factor (ANF) was determined in blood samples from the pulmonary artery simultaneously with recordings of right atrial, pulmonary arterial, pulmonary capillary wedge and systemic arterial pressures and heart rate during preload reduction with 0·5 mg nitroglycerin sublingually. Basal plasma ANF levels were higher in patients with congestive heart failure compared to normal controls, and correlated to right atrial, pulmonary arterial, and pulmonary capillary wedge pressures. After nitroglycerin all patients had reductions in right atrial, pulmonary arterial, and pulmonary capillary wedge pressures and a simultaneous decrease in plasma ANF concentrations, reaching lowest values after 10 min. Central pressures and plasma ANF rose to baseline values within 30 min. After nitroglycerin plasma ANF concentrations correlated to pulmonary arterial and pulmonary capillary wedge pressures, while changes in plasma ANF correlated to changes in right atrial and pulmonary arterial pressures. These results provide further evidence that ANF is released by a pressure-sensitive mechanism and demonstrates that ANF secretion in relation to central pressure variations is preserved in patients with congestive heart failure and that the response is rapid.     

Atrial natriuretic factor and central venous pressure during intermittent and continuous lower-body positive pressure in healthy humans

Summary. In eight healthy volunteers undergoing 16 experiments in a cross-over design central venous pressure (CVP) and atrial natriuretic factor (ANF) in central venous plasma were measured during a 30 min control period followed by three separated periods of 10 min lower-body positive pressure (LBPP) or 90 min continuous LBPP induced by inflation of a military anti-G suit to evaluate the effect of short repeated and of extended increases in right atrial pressure on plasma ANF levels. CVP increased significantly during each of three separate periods of intermittent LBPP, and 15 min after application of continuous LBPP (P<0·025 for all). Blood pressure and heart rate did not change. During intermittent LBPP plasma ANF levels increased 10 min after the first inflation of the MAGT-suit (P= 0·013), but not after the second or third inflation. During continuous LBPP plasma ANF remained unchanged until 90 min after application of LBPP where a significant rise was observed (P= 0·023). The data demonstrate that the ANF response to short-term increases in right atrial pressure, as small as 2·5 mmHg, is maximal within 10 min and that repeated pressure stimuli may decrease ANF release. Sustained increases in right atrial pressure are not associated with increases in plasma ANF until long after initiation of the pressure stimulus suggesting rapid receptor-binding of ANF and that the ANF receptors might be saturated during continuously elevated ANF levels.     

Atrial natriuretic factor during exercise in male endurance athletes: effect of training

Summary. Nine male endurance runners were evaluated with bicycle exercise testing before a training break of 3 weeks duration, and 0, 2 and 4 weeks after resumption of training to assess the effects of training on resting and exercise plasma atrial natriuretic factor (ANF) measured at 50% and 100% of predetermined maximal workload. Maximal oxygen uptake and lean body mass (LBM) were calculated at each time point. Maximal oxygen uptake decreased during training break, but rose 4 weeks after resumption of training (P<0·01). LBM was unchanged after inactivity, but rose after resumption of training (P<0·01). Plasma ANF at rest did not change throughout the experiment. ANF levels rose after training break at maximal workload (P<0·05), and decreased 4 weeks after resumption of training, but only at submaximal workload (P<0·05). No correlations between systolic blood pressure, mean blood pressure or heart rate and ANF could be demonstrated. These results indicate that the haemodynamic changes associated with endurance training are reflected in plasma ANF levels during exercise, but not at rest. The full adaptation of ANF release to training probably requires more time than the 4 weeks reported for the haemodynamic adjustments.     

Plasma levels of atrial natriuretic peptide at rest and during exercise in heart failure—influence of cardiac rhythm and haemodynamics

Summary. The relationship between plasma levels of immunoreactive atrial natriuretic peptide (ir-ANP), arginine vasopressin (AVP), cardiac rhythm and different haemodynamic variables were studied at rest and during exercise in 16 patients with heart failure undergoing heart catheterization for clinically indicated reasons. Even though there was no significant relationship between pulmonary capillary wedge pressure (PCW) and ir-ANP at rest (r= 0·39; P= 0·14) changes in these variables with exercise correlated well (r= 0·71; P= 0·002). Change in right atrial mean pressure, heart rate, mean arterial blood pressure or cardiac index did not significantly influence change in plasma levels of ir-ANP. The correlation between PCW and AVP at rest (r= 0·92; P<<0·001) disappeared during exercise. Calculated ir-ANP/PCW ratios decreased slightly during exercise, but were not influenced by initial atrial pressures or atrial fibrillation. These observations provide evidence for a similar responsiveness of ANP in patients with sinus rhythm and atrial fibrillation. The ability of rapid change in ANP plasma levels during exercise was preserved and proportional to changes in PCW over a wide pressure range in the studied patient group. This finding indicates that left atrium distension rather than right atrium distension is the major determinant for the release of ANP in patients with congestive heart failure. The observed rapid responsiveness of ANP to change in left atrial pressure may allow the hormone to modulate haemodynamic response during short periods of exercise.     

Changes in coronary haemodynamics and myocardial metabolism at rest and during exercise after a cardiotonic drug (prenalterol) in patients with coronary artery disease

Summary. To elucidiate the myocardial metabolic and haemodynamic effects of an inotropic drug in patients with coronary artery disease (CAD) without evident congestive heart failure (CHF), the acute effects of prenalterol were studied in nine patients. Patients with documented CAD by leftsided cardioangiography and end-diastolic pressure >15 mm Hg were included in the study. They were examined at rest and during supine exercise at a level just below their anginal threshold before and after prenalterol. At rest, rate pressure product (RPP) increased by 40% (P<0·01), cardiac index rose 20% (P<0·01), cardiac venous flow (CVF) increased by 18% (P<0·05), and myocardial oxygen consumption (MVO₂) increased by 20% (P<0·05) after prenalterol administration. Despite a decrease in mean pulmonary capillary venous pressure (PCV) of 40% (P<0·01), myocardial lactate extraction fell significantly (P<0·01) and lactate production was observed in three of nine patients compared to before prenalterol administration. During exercise, RPP increased by 20% (P<0·01), cardiac index remained unchanged, CVF increased by 25% (NS) and MV0₂ showed a tendency to an increase (NS) after prenalterol administration. Mean PCV pressure decreased by 30% (P<0·01). Myocardial lactate extraction was markedly reduced during exercise (P<0·01) and five of nine patients showed lactate production compared to that before prenalterol administration. Thus, despite a decrease in left ventricular filling pressure, increased myocardial oxygen demand occurred after acute administration of prenalterol. Prenalterol and probably similar inotropic drugs should be used cautiously in patients with CAD without clinical evidence of congestive heart failure.     

Significance of adrenoceptor-mediated atrial natriuretic factor release in normal humans.

To assess the potential role of adrenoceptor-stimulated atrial natriuretic factor (ANF) release in healthy humans, 18 volunteers, divided into groups of six, underwent experiments with infusion of incremental doses of salbutamol with and without beta-blockade with propranolol, propranolol alone, and bolus injections of clonidine before and after alpha-blockade with phentolamine, and phentolamine alone. Since changes in right atrial pressure have been shown to influence ANF release, central venous pressure (CVP) was continuously measured 30 min before, during the 120 min duration of drug infusions, and for 30 min after the bolus injections of the drugs. ANF was serially determined in central venous plasma during all drug infusions, and plasma catecholamines were measured to determine any possible influence of endogenous sympathetic activation on ANF levels. Plasma ANF was unaffected by all individual drugs and drug combinations, despite significant reductions in CVP in the salbutamol, phentolamine and phentolamine + clonidine groups, and a doubling of heart rate during salbutamol administration (p less than 0.01 for all). The results do not suggest a major role for adrenoceptor-mediated ANF release in normal humans, and do not indicate that plasma ANF levels are determined by tonic inhibition or facilitation of the sympathetic nervous system.     

Neuropeptide Y,noradrenaline and invasive haemodynamic data in mild to moderate chronic congestive heart failure

Summary. Neuropeptide Y (NPY) is a peptide released together with noradrenaline (NA) from sympathetic nerve endings. Elevated plasma levels of NA and NPY-like immunoreactivity (LI) are found in patients with congestive heart failure. In order to assess any relationship found between plasma NPY-LI and haemodynamic data 12 patients with mild to moderate chronic congestive heart failure were studied during cardiac catheterization. All patients were treated with diuretics but not ACE inhibitors and were in New York Heart Association functional class II or III. Mean left ventricular ejection fraction determined by echocardiography was 34%. Plasma NPY-LI from mixed venous blood was elevated in five patients and NA in nine. Mean plasma NPY-LI was 29±3pmoll^-1(mean±standard error of the mean) and NA2.6±0.3nmoll^-1. Heart rate was 70±3 beats min^-1, systolic blood pressure (SBP) 131 ±7 mmHg, stroke volume index (SVI) 29±l.9 ml m^-2 and cardiac index (CI) 2.0±0.13 1 min^-1 m^-2. Elevated levels of plasma NPY-LI (>30 pmol l^-1) were associated with lower SVI, CI, and SBP and a higher pulmonary vascular resistance. Elevated plasma NA (>2 nmol 1^-1) did not correlate with haemodynamic data. Log NPY-LI correlated inversely with SVI (P < 0.01) and CI (P < 0.05) but not with plasma NA. It is concluded that log NPY-LI in mixed venous blood correlates inversely with SVI and CI in patients with mild to moderate chronic congestive heart failure.     

Organ blood flow and distribution of cardiac output in dopexamine- or dobutamine-treated endotoxemic rats

Endotoxemia causes a decrease of blood flow to most organs. If this could be prevented, chances of survival might improve. In endotoxemic rats, we studied the effect of a therapeutic infusion of dopexamine (dopaminergic, β2-adrenergic) on blood flow and percentage of the cardiac output distributed to heart, brain, hepatic artery, stomach, intestines, spleen, pancreas, kidneys, adrenals, diaphragm, skeletal muscle, and skin. Dopexamine action was compared with that of dobutamine β1-adrenergic). Endotoxin shock was induced in 28 rats with infusion of 8 mg/kg Escherichia coli 0127:B8 endotoxin from 0 to 60 minutes; the rats were then divided into 3 groups, which received from 60 to 135 minutes of an infusion of saline (ES; n = 10), dopexamine hydrochloride (DX, 3.10⁻⁸ mol/kg · min; n = 10) or dobutamine (D8, 10⁻⁷ mol/kg · min; n = 8). A fourth group served as time-matched controls (C, saline from 0 to 135 minutes; n = 8). In the untreated endotoxemic rats, cardiac output decreased and organ blood flow decreased except in the diaphragm, heart, and brain; the percentage of the cardiac output to those organs increased. Dopexamine and dobutamine similarly improved cardiac output in endotoxemic rats. All organs benefitted to the same extent from the increased cardiac output. Therapeutic infusion of dopexamine during endotoxemia did not favor flow to any particular organ; redistribution of cardiac output changed little after administration of dopexamine, and its effects were not significantly different from those of dobutamine.     

Presence of choloyl- and chenodeoxycholoyl-coenzyme A thioesterase activity in human liver

The cardiac atria synthesize and store a hormone termed atrial natriuretic factor (ANF). ANF is released into the systemic circulation, and the circulating 28 amino acid peptide can be measured by radioimmunoassay. The hormone participates in body fluid homeostasis through its effect on renal sodium excretion and by inducing a shift of circulating fluid to the interstitial space. Release of ANF is mainly regulated by mechanical changes in the left and right atrial wall. It has been demonstrated that ANF release is related to changes in atrial wall tension occurring during each atrial cycle, and therefore, release of ANF will increase with increasing heart rate. Not only the increase in wall tension during passive atrial distension (v wave), but also the increase in tension during atrial systole (a wave) are determinants of ANF release. The mechano-chemical transducer is most likely located in the atrial myocytes, but its nature is unknown. There is no evidence to suggest that efferent cardiac nerves are essential in the regulation of ANF release. Humoral factors have been suggested as regulators of ANF release, particularly catecholamines and angiotensin II. A receptor-mediated direct stimulatory effect of a-adrenergic stimulation and an inhibitory effect of β-adrenergic stimulation have been demonstrated, but these direct effects are small compared to the effect of changes in atrial wall tension. Circulating catecholamines and angiotensin II stimulate ANF release mainly through their haemodynamic effects.     

Role of endogenous atrial natriuretic factor in acute congestive heart failure.

The current studies were designed to investigate the functional significance of elevated endogenous atrial natriuretic factor (ANF) in acute congestive heart failure (CHF). Integrated cardiorenal and endocrine function were measured in three models of acute low-output congestive heart failure with comparably reduced cardiac output (CO) and mean arterial pressure (MAP). Acute CHF was produced by rapid right ventricular pacing (group I, n = 5) which decreases CO and increases atrial pressures and plasma ANF. In group II, n = 5, thoracic inferior vena caval constriction (TIVCC) was produced to decrease venous return and CO but without increases in atrial pressure or plasma ANF. In group III, n = 5, TIVCC was performed and exogenous ANF infused to achieve plasma concentrations observed in acute CHF. In acute CHF with increases in endogenous ANF, sodium excretion (UNaV), renal blood flow (RBF), plasma renin activity (PRA), and plasma aldosterone (PA) were maintained despite decreases in CO and MAP. In contrast, TIVCC with similar reductions in CO and MAP but without increases in ANF resulted in decreases in UNaV and RBF and increases in PRA and PA. Exogenous administration of ANF in TIVCC to mimic levels in acute CHF prevented sodium retention, renal vasoconstriction, and activation of renin and aldosterone. These studies demonstrate that endogenous ANF serves as an important physiologic volume regulator in acute CHF to maintain sodium excretion and possibly participate in the suppression of activation of the renin-angiotensin-aldosterone system despite the stimulus of arterial hypotension.     

Right ventricular myocardial isovolumic relaxation time and pulmonary pressure

Aims: Non‐invasive assessment of pulmonary artery systolic pressure (PASP) has several limitations. As previously described by Burstin, the right ventricular (RV) isovolumic relaxation time (IVRt) is sensitive to changes in PASP. We therefore compared RV myocardial IVRt, derived by Doppler tissue imaging (DTI), with simultaneously measured invasive PASP. Methods and results: Twenty‐six consecutive patients (18 males, mean age 52 ± 12 years, range 23–75) underwent a simultaneous Doppler echocardiography, including DTI, and cardiac catheterization examination for measurement of PASP and right atrial mean pressures. IVRt was measured using the myocardial velocities by pulsed DTI at both basal and mid cavity segments of the RV free wall. As diastolic time intervals are influenced by heart rate IVRt was corrected for heart rate (IVRt/RR%). A significant correlation was found between PASP and regional IVRt/RR% at both the basal (r = 0·42, P<0·05) and mid cavity segment (r = 0·71, P<0·001). Furthermore, when only patients with normal right atrial pressures (<7 mmHg) were taken into account, the correlation coefficient improved at both basal and mid cavity segments (r = 0·74, P<0·05 and r = 0·83, P<0·01). Conclusion: Pulsed Doppler‐derived IVRt correlates well with PASP. The use of pulsed DTI for measurement of IVRt is simple, reproducible and easy to obtain. We propose this method as an additional non‐invasive tool in the assessment of PASP.     

Cardiovascular functioning during the menstrual cycle

Variations in cardiovascular functioning during the ‘normal’ menstrual cycle have been little researched. Resting‐blood pressures, resting‐heart rate, rate‐pressure product (RPP) and a derived index of fitness (Schneider Index) were monitored throughout natural, hormonally defined menstrual cycles. Volunteers were 26 women (20–48 years) who had regular (25–35 days) cycles. Their blood pressures and heart rate (at rest and according to Schneider’s protocol) were measured at the same time daily (Monday–Friday) for 5 weeks. Daily, early morning‐urine samples were assayed for sex hormones enabling accurate definition of cycle phase for each woman. Resting systolic‐blood pressure was significantly higher in the ovulatory phase (P<0·05) than in the follicular or luteal phases, but resting‐diastolic pressures did not differ significantly between phases. Resting‐heart rate was significantly higher in both ovulatory (P<0·01) and luteal (P<0·01) phases than in the menstrual and follicular phases. The Schneider Index was higher during the follicular phase than during the ovulatory (P<0·005) or luteal (P<0·01) phases, the RPP was higher during the ovulatory phase than during the bleeding (P<0·05) and follicular (P<0·005) phases. These findings provide a pattern of menstrual cycle‐related variation in cardiovascular functioning that can be related to established actions of the ovarian steroids.     

Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema.

Atrial natriuretic factor (ANF), a recently sequenced cardiac peptide, has been shown to have potent natriuretic, diuretic, and vasodilating effects in several species. We have developed a radioimmunoassay to measure the levels of immunoreactive ANF in human plasma. Plasma levels of ANF in healthy volunteers on a low sodium diet were 9.8 +/- 1.4 pmol/liter and increased to 21.9 +/- 3.0 on a high sodium diet. The levels of atrial natriuretic factor correlated directly with urinary sodium and inversely with plasma renin activity and plasma aldosterone levels. Patients with marked edema due to congestive heart failure had plasma levels of atrial natriuretic factor five times higher than normal (P less than 0.05), whereas patients with cirrhosis and edema had levels that were not different from normal. These results suggest that atrial natriuretic factor plays an important role in the adaptation to increased sodium intake.     

The Effect of Liver Extract in Cultures of Megaloblastic Bone Marrow

N-terminal (atrial natriuretic factor (ANF) 1-98) and C-terminal (ANF 99-126) fragments of proatrial natriuretic factor (NTA and CTA, respectively) were determined in plasma of healthy subjects adopting different postures and in patients with cirrhosis. Seven healthy subjects were investigated while seated and 30 min after assuming a horizontal position. NTA plasma concentrations increased in subjects in the horizontal position (from 734±250 (SE) fmol/ml to 9021227 fmol/ml; p<0.05). In contrast, CTA plasma concentrations remained unchanged (9.2+1.3 fmol/ml vs 8.9±1.6 fmol/ml). In 10 patients with cirrhosis of the liver, NTA concentrations were markedly (p<0.001) elevated compared to 11 healthy subjects (2334±291 fmol/ml vs 743±155 fmol/ml). However, there was no difference of CTA plasma levels between cirrhotic patients and healthy subjects (8.7±1.3 fmol/ml vs 8.2±0.9 fmol/ml). These data demonstrate changes of the plasma concentration of the N-terminal fragment of proatrial natriuretic factor by posture and in liver disease, in contrast to unchanged levels of the C-terminal fragment.     

Atrial natriuretic factor has a weak insulinotropic action in the isolated perfused rat pancreas

The effect of atrial natriuretic factor (ANF; 1, 10, 100, 1000 pmol/l) on insulin release from the isolated perfused rat pancreas was studied. ANF weakly augmented the glucose (10 mmol/l)-stimulated insulin release during the second (controls: 100%; 1 pmol/l: 99%; 10 pmol/l: 149%, P<0.05; 100 pmol/l: 111%; 1000 pmol/l 135%), but not the first phase of the secretory response. In contrast, the first, but not the second phase of arginine (10 mmol/l)-stimulated insulin release was significantly enhanced by ANF (1000 pmol/l; controls: 100%; 1000 pmol/l: 235%, P<0.05). The hormone did not influence basal insulin secretion. Our data indicate an insulinotropic effect of ANF on the rat pancreas, which is dependent on the utilized background secretagogues.     

Chronotropic incompetence response to exercise in congestive heart failure,relationship with the cardiac autonomic status

In chronic congestive heart failure (CHF), attenuated heart rate response to exercise, a manifestation of chronotropic incompetence (CI), contributes to limiting exercise capacity. The present study was thus conducted to evaluate the respective role of chronic attenuation of cardiac vagal tone associated with depressed baroreflex sensitivity or affected cardiac sympathetic responsiveness in CHF patients with CI. Spontaneous cardiac baroreflex sensitivity (BRS) assessed by sequence method and spectral‐ and time‐domain analysis of heart rate variability (HRV) were analysed in 21 chronic CHF patients. All patients performed a symptom‐limited exercise test with measurement of gas exchange. Chronic incompetence which was defined as failure to achieve ≥80% of the heart rate reserve (%HRR) given by (HR_peak – HR_rest)/(predictive maximal heart rate – HR_rest) was observed in 14 (66%) patients. There was no significant difference in age, heart rate, peak oxygen uptake or left ventricular ejection fraction between the patients with and without CI. Although there was no significant difference in BRS, low frequency power of HRV in normalized units (LFnu) and SDNN were significantly lower in CI patients. Percentage of HRR correlated significantly with LFnu on 15 min (r=0·64, P<0·005) and, with LFnu on 24 h (r=0·52, P<0·01), SDNN (r=0·48, P=0·03) and SDANN (r=0·48, P=0·03), but not BRS (r=0·04, P=NS). Autonomic nervous system derangement is a complex process in CHF. The role of basal depressed cardiac sympathetic tone seems to contribute more closely than depressed baroreflex sensitivity to the impaired heart rate response to exercise frequently observed in CHF patients.     

Effect of vasoactive intestinal polypeptide (VIP) on pulmonary ventilation-perfusion relationships and central haemodynamics in healthy subjects,

Summary. Ventilation-perfusion relationships of the lung (VA/Q) and central haemodynamics were studied in nine healthy subjects before and during 30 min of vasoactive intestinal polypeptide (VIP) infusion (20 ng kg-min^-1). During the infusion, arterial concentrations of VIP rose from 16-1 6-1 to 420 110 pmol 1^-1 and noradrenaline concentrations doubled (P < 0–01). VA/Q distributions, determined by inert gas elimination technique, were significantly shifted to lower values for VA/Q with slight increases in dispersions, but arterial oxygen tension remained unchanged. Heart rate, stroke volume and cardiac output rose 27, 44 and 80% respectively (P < 0–01). Systematic arterial pressure stabilized at a slightly lower level compared to basal (base line: 93 5 mmHg, VIP: 88 6 mmHg, P < 0–05). Right atrial and pulmonary capillary wedge pressures remained unchanged during VIP infusion, while pulmonary vascular resistance and systematic vascular resistance decreased significantly, by 25% (P < 0–03) and 53% (P < 0–01), respectively. It is concluded that VIP causes: (1) alterations in ventilation-perfusion distributions, but generates no shunt and does not cause hypoxaemia during 30 min infusion, (2) reduction of pulmonary and systemic vascular resistances and afterload reduction of the left ventricle, (3) reflex sympathoadrenal stimulation with increasing heart rate and myocardial contractility, and (4) a direct positive inotropic effect on the myocardium.     

Hemodynamic effects of isoproterenol and norepinephrine in acute cardiac tamponade

The hemodynamic effects of isoproterenol infusion, 0.5 μg/kg per min were evaluated in eight intact anesthetized dogs during cardiac tamponade. During tamponade, the mean of pericardial pressures was increased from — 1.5 to 12.5 mm Hg, and the mean of right atrial pressures was increased from 1 to 12.4 mm Hg. Mean cardiac output fell from 144.8 to 44.8 ml/kg per min (P < 0.001), and rose to 105.6 ml/kg per min (P < 0.001) with isoproterenol. Mean cardiac stroke volume fell from 20.3 to 6.1 ml during tamponade (P < 0.001) and rose to 12.1 ml with isoproterenol (P < 0.001). The heart rate increased from 193.3 beats/min during tamponade to 217.5 beats/min with isoproterenol (P < 0.05). During isoproterenol infusion, the mean right atrial pressure and mean pericardial pressure decreased significantly. With cardiac tamponade, the mean blood pressure fell from 157.5 to 126.1 mm Hg (P < 0.01) and did not change significantly with isoproterenol, 11 additional animals were studied with norepinephrine infusion during tamponade. There were no consistent hemodynamic effects with infusions of 0.5 and 1 μg/kg per min. With norepinephrine 2, 5, and 10 μg/kg per min cardiac output rose in some experiments. Isoproterenol infusion increased the cardiac output during tamponade principally by increasing cardiac stroke volume and to a lesser degree by increasing the heart rate. It is postulated that the increased stroke volume resulted from an increased ejection fraction with greater decrease in end-systolic than end-diastolic ventricular volume. These effects are consistent with the known positive inotropic, peripheral vasodilator, and positive chronotropic effects of isoproterenol.     

Adrenergic control of plasma magnesium in man

Regulation of magnesium balance is poorly understood. However, hypomagnesaemia has been reported in patients in clinical situations where circulating catecholamines are raised including myocardial infarction, cardiac surgery and insulin-induced hypoglycaemia stress tests. The effects of L-adrenaline infusions, sufficient to achieve pathophysiological levels of adrenaline, and of therapeutic intravenous infusions of salbutamol, a beta 2-agonist, on plasma magnesium, plasma potassium, plasma glucose and plasma insulin levels were studied in a placebo-controlled design in eight normal subjects. Plasma magnesium levels fell significantly during the adrenaline infusion and also during the salbutamol infusion, though more slowly. In a 1 h period of observation after cessation of the infusions no recovery of plasma magnesium levels was seen. Significant falls in plasma potassium levels were also observed during both infusions with spontaneous recovery within 30 min after the infusions. No significant changes in plasma insulin levels occurred with either salbutamol or L-adrenaline compared with control. Plasma glucose levels rose significantly during the adrenaline infusion. The study suggests that both L-adrenaline and salbutamol cause shifts in plasma magnesium which are not mediated by insulin. We propose that intracellular shifts of magnesium occur as a result of beta-adrenergic stimulation.     

Physiological effects of synthetic atrial natriuretic factor in normal conscious dogs

The objective of this study was to examine the integrative physiologic effects of atrial natriuretic factor (ANF). Synthetic 99-126 ANF was administered to 6 normal conscious dogs as two consecutive infusions (0.02 and 0.1 microgram/kg/min respectively) each over 30 min: each infusion was preceded by a priming dose of 1 microgram/kg. With the first infusion, mean arterial pressure declined from 113 +/- 2 to 103 +/- 4 mmHg, pulmonary capillary wedge pressure declined from 9.6 +/- 0.5 to 7.2 +/- 0.7 mmHg and right atrial pressure declined from 9.8 +/- 0.4 to 8.0 +/- 0.7 mmHg (all p less than 0.05). No change in heart rate was seen. Despite very high plasma ANF concentrations, no further decline in arterial or central filling pressures were seen in the second infusion. In contrast, cardiac output declined progressively from 3.8 +/- 0.2 to 2.8 +/- 0.21/min (p less than 0.01) by the end of second infusion. Plasma renin activity declined from 2.2 +/- 0.7 to 0.9 +/- 0.3 ng/ml/hr (p less than 0.05) while plasma norepinephrine remained unchanged. Urine output and sodium excretion increased in a dose dependent manner. The diverse time course of the hemodynamic, renal and neuroendocrine effects suggests these effects of ANF are mediated by different mechanisms. Furthermore, the failure of heart rate and plasma norepinephrine to increase despite a significant decline in blood pressure and cardiac output suggests ANF may have a depressant effect on the sympathetic nervous system.