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The diuretic and natriuretic responses to stimulation of atrial receptors were compared in two groups of anaesthetized dogs, one group with a high blood volume and another group with a low blood volume. A diuretic response to stimulation of the atrial receptors was obtained in the two groups of animals. Both the diuretic and the natriuretic responses to stimulation of the atrial receptors were greater in the dogs with high blood volume than in the dogs with low blood volume. In a second series of experiments, a diuretic response to stimulation of the atrial receptors was demonstrated in both groups of animals following surgical denervation of the kidney. In the denervated kidney, a large increase in heart rate, associated with stimulation of the atrial receptors, significantly contributed to the diuretic response in the dogs with high blood volume but not to the response in dogs with low blood volume. In the denervated kidney, a natriuretic response was only obtained in the dogs with high blood volume in which a large increase in heart rate was associated with stimulation of the atrial receptors. The present results show that the diuretic and natriuretic responses to stimulation of atrial receptors are greater in dogs with high blood volume than in dogs with low blood volume, and that increases in heart rate, associated with stimulation of atrial receptors, significantly contribute to the diuretic and natriuretic responses in acutely denervated kidneys in the dogs with high blood volume.

Stimulation of atrial receptors by distension of a balloon in the left atrium of anaesthetized dogs results in a reflex diuresis mediated by an unknown humoral agent. This paper reports the further purification from plasma of acetone extracts of the humoral agent which may mediate the diuretic response. Activity of the humoral agent was detected using the Malpighian tubules of Rhodnius prolixus. Gel filtration of the acetone extracts on Sephadex G-25 and G-100, followed by dialysis of the fraction from Sephadex G-100 that contained the humoral agent, showed that the activity of the agent was associated with a high molecular weight fraction (greater than 30000). Acetone extracts of the humoral agent were also shown to be stable to treatment with HCl for 1 h at 25 degrees C. After this acid treatment, gel filtration on Sephadex gels and Bio-Gel P-2 showed that the agent was of low molecular weight (less than 1800). It is concluded that the activity of the humoral agent, as detected by the Malpighian tubule preparation, is associated with a molecule of low molecular weight which may be bound to a larger molecule from which it can be dissociated by acid treatment.

The diuretic response to stimulation of left atrial receptors by distending small balloons located at the pulmonary vein--left atrial junctions and in the left atrial appendage was studied in anaesthetized dogs in which bretylium tosylate, atenolol and atropine had been administered to effect blockade of renal nerves and to prevent increases in heart rate resulting from stimulation of atrial receptors. In these dogs, distension of the balloons was not associated with significant changes in heart rate, left atrial pressure or arterial blood pressure, and resulted in increases in urine flow, decreases in urinary sodium concentration and no significant changes in urinary sodium excretion. It is concluded that the humoral mechanism is responsible for the diuresis in response to stimulation of atrial receptors and has no significant effect on the response of natriuresis known to involve a decrease in the activity in the renal nerves and haemodynamic changes associated with stimulation of atrial receptors.

In dogs anaesthetized with alpha-chloralose the effects of distension of a large balloon in the lumen of the left atrium on the discharge of action potentials in vagal fibres and on urine flow were studied with the cervical vagi cooled at 18 and 12 degrees C. Distension of the balloon in seven dogs resulted in an increase in urine flow. Cooling the cervical vagi to 18 degrees C reduced the response to 70% of that obtained at 37 degrees C, and at 12 degrees C the response was reduced to 28%. In a second group of dogs, the effect of distension of the balloon on atrial receptors which discharged into myelinated nerve fibres of the vagi, i.e. Paintal type A and type B receptors, was examined. The increase in the activity of these receptors was reduced to 68% when the vagus nerve was cooled to 18 degrees C and was reduced further to 25% at 12 degrees C., In a third group of dogs, the effect of distension of the balloon on receptors which discharged into non-myelinated nerve fibres in the vagi was examined. Cooling of the cervical vagi also reduced the evoked increase in activity in these fibres; this reduction in activity occurred over a wider range of temperature, unlike the effect of cooling on the response in myelinated vagal fibres. It is concluded that the increase in urine flow caused by distension of a balloon in the left atrium is mediated solely by the Paintal-type atrial receptors which discharge into the myelinated fibres in the vagi.

Stimulation of left atrial receptors causes a diuresis partly through a blood borne agent. Malpighian tubules of Rhodnius prolixus can detect a blood borne agent during the diuresis. It has been suggested that the agent is ADH but this is in dispute. In the present investigation, vasopressin (1-300 mu i.u. cm-3) was found to have no effect on Malpighian tubule secretion when added to plasma, Rhodnius Ringer and Rhodnius Ringer + 5-HT. In addition, it was shown that incubation with sodium thioglycollate of plasma samples obtained from anaesthetized dogs, before and during stimulation of atrial receptors by distension of a balloon in the lumen of the left atrium, did not abolish the differences between test and control plasma samples detected by the Malpighian tubules. It is concluded that differences in plasma detected by the Malpighian tubules and related to the diuresis which results from left atrial stimulation are not attributable to changes in concentration of ADH.

Stimulation of atrial receptors in anaesthetized dogs results in a reflex increase in urine flow mediated by vagal myelinated fibres and, in part, by a humoral agent of unknown identity. The humoral agent has been detected by an in vitro preparation of the Malpighian tubules of Rhodnius prolixus. The purpose of this investigation was to determine whether the present extract of plasma purporting to contain the humoral agent is also related to the reflex diuresis. In nine chloralose anaesthetized dogs atrial receptors were stimulated by distension of a balloon in the left atrium. Plasma samples collected before and during distension of the balloon, respectively, were precipitated with acetone, acid-treated and fractionated on Bio-Gel P-2. The purified samples were tested for the activity of the humoral agent on the Malpighian tubule preparation. In each dog, distensions of the balloon were performed with the cervical vagal nerves at 9 and 37 degrees C. Cooling the vagal nerves to 9 degrees C abolished the reflex diuresis and abolished the activity of the humoral agent recovered from a Bio-Gel P-2 fraction (molecular weight range 100-1800) which elutes between the void volume and the salt fraction. It was concluded that the substance recovered from Bio-Gel P-2 is associated with the diuresis in response to stimulation of atrial receptors; it is suggested that its presence is dependent on the integrity of the afferent limb of the atrial receptor reflex.

The diuretic response to stimulation of left atrial receptors, by distending balloons located either at the pulmonary vein-left atrial junctions or in the body of the left atrium was studied during blockade of dopamine receptors using a continuous infusion o sulpiride in doses ranging from 0.632 to 5.153 mumol . kg-1 . min-1, in anaesthetized dogs. A diuretic response was obtained in each experiment of distension of the balloons: the response was similar to that observed in dogs without blockade of dopamine receptors and was not significantly related to the dose os sulpiride used. It is concluded that the diuretic response to stimulation of atrial receptors, known to be mediated by a blood-borne agent, is unlikely to be caused by dopamine.

Stimulation of atrial receptors by distension of a balloon in the left atrium of anaesthetized dogs results in a reflex diuresis mediated by a humoral agent of unknown identity. In previous investigations, a substance was recovered in a low molecular weight fraction from Bio-Gel P-2 (100-1800 daltons) and shown to be related to the reflex diuresis. In this investigation, the active Bio-Gel P-2 fraction was partitioned with ethyl acetate at pH 11.0, with subsequent partition of the aqueous phase with ethyl acetate at pH 7.4; the activity of the humoral agent was soluble in ethyl acetate at pH 7.4. These investigations suggest that the humoral agent is a low molecular weight, lipophilic and weakly acidic substance. The substance is not antidiuretic hormone (ADH) as vasopressin is insoluble in ethyl acetate at pH 7.4.

1. Stimulation of left atrial receptors by distension of a balloon in the lumen of the left atrium of anaesthetized dogs was shown to result in an increase in urine flow. Plasma samples obtained from these dogs during control periods and during periods of stimulation were applied to the Malpighian tubules of Rhodnius prolixus. 2. It was found that the tubules suspended in test plasma secreted at a significantly lower rate than those suspended in control plasma. 3. These differences were also evident in extracts of plasma prepared using the solvent n-butanol. 4. Cutting or cooling the cervical vagi abolished these differences along with the increase in urine flow. It is argued that this preparation of the Malpighian tubule of Rhodnius prolixus could be used as a means of detecting the diuretic agent responsible for the increase in urine flow.

The diuretic response to stimulation of left atrial receptors, by distending balloons located either at the pulmonary vein-left atrial junctions or in the body of the left atrium, was studied during blockade of the generation of angiotensin II using a continuous infusion of angiotensin converting enzyme inhibitor, SQ 14,225, in anaesthetized dogs. Despite blockade of angiotensin conversion, known also to potentiate the activity of bradykinin, a diuretic response was obtained in each dog; the response was similar to that observed in dogs without blockade of angiotensin conversion. Angiotensin II and bradykinin did not significantly influence the rate of secretion of Malpighian tubules of Rhodnius prolixus, which have been shown capable of detecting the blood-borne agent known to mediate the diuretic response. It is concluded that neither angiotensin II nor bradykinin is likely to be the blood-borne agent released by stimulation of atrial receptors.

The diuretic response to stimulation of left atrial receptors by distending balloons located either at the pulmonary vein-left atrial junctions or in the body of the left atrium, was studied in anaesthetized dogs in which on kidney had been surgically denervated. In these dogs diuretic and natriuretic responses to stimulation of atrial receptors were obtained in the denervated and the intact kidney; both responses were significantly greater in the intact kidney than in the denervated kidney. In the denervated kidney the natriuretic response showed a significant correlation to increases in heart rate resulting from stimulating of atrial receptors. It is concluded that the renal nerves contribute significantly to the increases in urine flow and sodium excretion in response to stimulation of atrial receptors. In the denervated kidney, the diuresis appeared to be mediated by a humoral mechanism and the natriuresis was associated with concomitant increases in heart rate.

1. In anaesthetized dogs, stimulation of atrial receptors after destruction of the pituitary gland results in a diuresis. This response was not abolished by the administration of bretylium tosylate and was also observed in a surgically denervated kidney. 2. The diuresis is qualitatively similar to that observed in anaesthetized dogs with intact pituitary glands. 3. It is concluded that the diuresis which results from stimulation of the left atrial receptors is mediated by a blood-borne agent which is not the antidiuretic hormone.

Stimulation of left atrial receptors in dogs anaesthetized with chloralose results in a reflex diuresis and a small decrease in the plasma concentration of vasopressin. It has been suggested that this diuretic response is solely mediated by the antidiuretic hormone, vasopressin (Gauer & Henry, 1976; Ledsome, 1985). The present investigation was designed to determine how these anaesthetized dogs, which are thought to be insensitive to changes in plasma vasopressin, respond to small decreases in plasma vasopressin similar to those observed during stimulation of left atrial receptors. In the event it was shown for the first time that it is possible to obtain a water diuresis in an anaesthetized animal in response to a small fall in the concentration of plasma vasopressin. In order to produce changes in plasma vasopressin similar to those seen during stimulation of left atrial receptors the pituitary gland was removed and an intravenous infusion of arginine vasopressin was given in eleven dogs anaesthetized with chloralose; a small decrease in plasma vasopressin was then produced by replacing the vasopressin with an infusion of saline for 30 min. A decrease in the plasma concentration of 1.29 pg cm-3 from a control concentration of 1.85 pg cm-3 resulted in a 96.7% increase in urine flow. The fall in concentration of vasopressin consequent upon stimulation of atrial receptors could, therefore, explain the water diuresis in the anaesthetized dog preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of increasing heart rate by increasing the rate of atrial pacing in the absence of any reflex effects from atrial receptors, by cooling the vagi to 12 degrees C, was studied in two groups of dogs with different blood volumes. In one group of nine dogs with a high blood volume increasing heart rate, by an amount similar to that reflexly obtained in response to stimulation of atrial receptors, resulted in significant increases in urine flow and sodium excretion; in another group of eight dogs with a low blood volume similar increases in heart rate did not result in a diuresis or natriuresis. The findings suggest that the effects of an increase in heart rate in combination with differences in blood volume could contribute to the previously reported differences in the urinary responses that result from stimulation of atrial receptors in dogs with different blood volumes.

This paper reports the initial purification steps of a humoral agent which may mediate the diuresis resulting from stimulation of left atrial receptors in anaesthetized dogs. The agent was shown to be stabilized in plasma by acidification to pH 3.2. Acid acetone precipitation was found to be a convenient method as a first stage in the purification of the humoral agent in plasma. Heat stability studies showed that the agent was stable in acidified plasma for up to 20 min of heating in a boiling water bath. Precipitation of plasma proteins under these conditions made this another possible first stage in the purification of the agent in plasma. Some general conclusions about the possible nature of the humoral agent are discussed.

Stimulation of the left atrial receptors in dogs anaesthetized with chloralose results in a reflex diuresis and natriuresis. The efferent limb of this reflex is though to have at least three components: nervous, haemodynamic and humoral. The present study was designed to investigate the humoral component in dogs anaesthetized with chloralose; to determine whether a humoral agent, other than vasopressin, might be causative in this reflex diuresis. The nervous and haemodynamic components were prevented by pharmacological denervation. Any possible contribution to the diuresis by a decrease in the plasma concentration of vasopressin was prevented by the removal of the pituitary gland. In animals in which a spontaneous diuresis followed hypophysectomy, an infusion of arginine vasopressin sufficient to maintain urine flow in the normal range for these dogs anaesthetized with chloralose was given. Distension of small balloons at the pulmonary vein-atrial junctions and in the left atrial appendage discretely to stimulate the atrial receptors in eleven dogs anaesthetized with chloralose resulted in a significant diuresis. It was concluded that a blood-borne agent other than vasopressin was responsible for the observed diuresis. At the moment it is not known whether vasopressin or the diuretic agent, or both, are involved in the diuresis accompanying the stimulation of atrial receptors.

1. Distension of the atrial appendages resulted in a diuresis, an increase in the rate of Na(+) excretion and an increase in heart rate.2. Both the urinary and heart rate responses to distension of the appendages were either abolished or much reduced by crushing the bases of the appendages.3. The diuresis in response to distension of the atrial appendages is similar to that previously described in response to distension of the pulmonary vein-atrial junctions by Ledsome & Linden (1968).4. It is concluded that stimulation of nerve endings within the atrial appendages results in a reflex increase in urine flow and heart rate.

1. Complex unencapsulated nerve endings (right atrial receptors) have previously been found in the endocardium of the right atrial appendage and the junction between the superior vena cava and the right atrium.2. Distension of balloons located in the right atrial appendage and at the junction between the superior vena cava and the right atrium resulted in an increase in urine flow. This diuresis was accompanied by a small increase in the excretion of sodium.3. Cooling the right cervical vagus caused a reduction in the response to distension of the right atrial appendage.4. It is concluded that stimulation of right atrial receptors by the distension of balloons located in the right atrial appendage and at the junction between the right atrium and the superior vena cava results in a reflex increase in urine flow.

1. 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.