No abstract

SUMMARY1. The diuretic response to distension of the whole left atrium caused by obstruction of the mitral orifice has been compared with the effects of distension (by means of small balloons) of the left pulmonary vein/left atrial junctions.2. Distension of the pulmonary vein/atrial junctions caused an increase in heart rate and a diuresis similar to but smaller than that caused by mitral obstruction.3. Section of both ansae subclaviae prevented the increase in heart rate produced by distension of the pulmonary vein/left atrial junctions but had little effect on the diuretic response either to pulmonary vein distension or to mitral obstruction. 4. A diuretic response to mitral obstruction could be demonstrated after all nerves from the lungs had been cut but not after the vagus nerves had been cut at levels likely to interrupt the majority of afferent fibres from left atrial receptors.5. The results support the view that stimulation of left atrial receptors is a major factor in the production of a diuretic response to mitral obstruction.

Recent reviewers primarily interested in renal (Smith, 1957) and cardiovascular physiology (Neil, 1960) have accepted a theory that distension of the left atrium of the heart sets up afferent impulses in the vagus nerves which decrease the release of antidiuretic hormone from the neurohypophysis, and so cause diuresis. The theory is within the general conception that the renal excretion of water and electrolytes is partly governed by the volume in some fluid compartment of the body. Support for this role of atrial receptors has been derived from the experiments of Henry, , who found that in anaesthetized dogs inflation of a balloon in the left atrium caused an increase in urine flow with a time course and other characteristics which could be accounted for by a diminished release of antidiuretic hormone. The paper of contains little evidence to support this interpretation. In view of the theoretical importance attached to them the experiments have been repeated and extended in this paper; whilst the main results are confirmed, the small and variable size of the response is emphasized and additional observations make untenable the explanation that the diuresis is due to decreased release of antidiuretic hormone. A preliminary account has already been published (Ledsome, Linden & O'Connor, 1961). METHODSThe experiments were carried out as described by . Dogs of 10-15 kg were given 15 mg morphine sulphate by subcutaneous injection and 1 hr later were anaesthetized by the intravenous infusion of 1 % chloralose (British Drug Houses; 10 ml. = 0-1 g/kg) in sodium chloride solution 0-6 g/100 ml. Subsequently during the experimental procedures a steady state of light anaesthesia was maintained by the infusion every 10 min of either 1 or 0 5 % chloralose, about 1 ml./kg. Each ureter was catheterized through a flank incision into the peritoneal cavity, and urine volume was measured every 10 min collected urine from a urethral catheter). With the animal under positive-pressure ventilation from a Starling 'Ideal' Pump, the chest was opened in the left fifth intercostal space, and a balloon inserted into the left atrium through the appendage in which it was secured by a ligature. The chest was closed, air expelled through a drainage tube in the 7th intercostal space and normal respiration restored. The operative

A heterologous radioimmunoassay was used to measure the concentration of immunoreactive atrial natriuretic peptide (iANP) in plasma from the femoral artery of eight chloralose anaesthetized dogs. Mitral obstruction which increased left atrial pressure by 11 cmH2O increased plasma iANP from 97 +/- 10.3 (mean +/- SE) to 135 +/- 14.3 pg/mL. Pulmonary vein distension increased heart rate but did not increase plasma iANP. Bilateral cervical vagotomy and administration of atenolol (2 mg/kg) did not prevent the increase in iANP with mitral obstruction. Samples of blood from the coronary sinus had plasma iANP significantly higher than simultaneous samples from the femoral artery confirming the cardiac origin of the iANP. Release of iANP depends on direct stretch of the atrium rather than on a reflex involving left atrial receptors.

1. Small balloons were inserted through the left pulmonary veins so as to lie at the pulmonary vein-left atrial junctions.2. Distension of the balloons caused a reflex increase in heart rate. The afferent path was in the vagus nerves and the efferent path was in the cardiac sympathetic nerves.3. Only small and variable changes in vascular resistance in a perfused hind limb accompanied the increase in heart rate when a steady state had been reached.4. In about half of the experiments a transient vasodilatation was observed in the perfused hind limb, occurring immediately after distension of the pulmonary vein-atrial junctions and lasting about 22 sec.5. The transient dilatation was due to a decrease in sympathetic vasoconstrictor nervous activity.6. Stimulation of left atrial receptors causes an increase of sympathetic nervous activity to the heart but does not cause a corresponding increase in sympathetic nervous activity to the hind limbs.