Cardiovascular afferent signals and drinking in response to hypotension in dogs.

Arterial hypotension stimulates increases in plasma arginine vasopressin (AVP), plasma renin activity (PRA), and water intake in conscious dogs. We have previously reported that increasing left atrial but not right atrial pressure completely blocks the increase in plasma AVP and PRA induced by hypotension. The goal of the present study was to examine the effect of increasing right or left atrial pressure on water intake induced by arterial hypotension. Dogs were prepared with occluding cuffs on the thoracic inferior vena cava, the pulmonary artery, and the ascending aorta. We reduced mean arterial pressure (MAP) 25% below control by either inferior vena cava constriction (IVCC), pulmonary artery constriction (PAC), or ascending aorta constriction (AAC) and measured water intake over a 2-h period. Cumulative water intake during IVCC (n = 6) and PAC (n = 6) was 7.8 +/- 2.0 and 6.7 +/- 2.6 ml/kg, respectively. There was no difference between either the latency or the volume consumed between the two treatments. In contrast, none of the dogs drank during hypotension induced by AAC (n = 5). Because the degree of arterial baroreceptor unloading was the same in each treatment by design, we conclude that stimulation of left atrial receptors inhibits drinking in response to arterial hypotension but that stimulation of right atrial receptors has no effect on the response in dogs.

Effect of loading right atrial and ventricular receptors on stimulated AVP, ACTH, and renin secretion in awake dogs.

The goal of this study was to test the hypothesis that increasing or decreasing the load on baroreceptors in the right heart influenced the secretion of arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH), and renin during a state of sustained arterial hypotension. The hypothesis was tested in chronically instrumented conscious dogs prepared with inflatable cuffs around the pulmonary artery (PA) and the thoracic inferior vena cava (IVC). In one protocol (n = 5), mean arterial pressure was reduced 10 or 20% below control by constriction of the PA, a maneuver that caused a fall in left atrial pressure (LAP) and an increase in right atrial pressure (RAP). Plasma AVP, ACTH, atrial natriuretic peptide (ANP), and plasma renin activity (PRA) all increased (P < 0.05) in response to constriction of the PA. Reducing RAP to control by constriction of the IVC during maintained constriction of the PA had no effect on MAP, LAP, plasma AVP, ACTH, or PRA, but plasma ANP fell significantly. In a separate protocol (n = 4), constriction of the IVC was used to reduce MAP 10 or 20% below control, and this led to significant decreases in both LAP and RAP and increases in plasma AVP, ACTH, and PRA. RAP was then increased above control by constriction of the PA without altering either MAP or LAP. Raising RAP from a level that was 6.3 +/- 1.3 mmHg below control to 3.5 +/- 1.0 mmHg above control had no effect on plasma AVP, ACTH, or PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Left heart and arterial baroreceptors interact in control of plasma vasopressin, renin, and cortisol in awake dogs.

Arterial hypotension induced by constriction of the ascending aorta (AA) causes increases in left atrial pressure (LAP) and plasma atrial natriuretic peptide (ANP), but no change in plasma arginine vasopressin (AVP), plasma renin activity (PRA), or cortisol. In the present study, we tested the hypothesis that the rise in left heart pressure during constriction of the AA suppressed the stimulation of AVP, renin, and cortisol secretion in response to arterial hypotension. Dogs were prepared with inflatable cuffs around the AA, the pulmonary artery (PA), and the thoracic inferior vena cava (IVC) and with catheters in the left and right atria and abdominal aorta. In one series of experiments, the AA was constricted to lower mean arterial pressure (MAP) 10 or 20% below control for 15 min. Then, either the PA or the IVC was constricted to bring LAP back to control levels but without altering the degree of arterial hypotension. Constriction of the AA alone led to significant increases in LAP and plasma ANP but no change in plasma AVP, cortisol, or PRA. Reducing LAP to control levels by constriction of either the PA or IVC led to significant and similar increases in plasma AVP, cortisol, and PRA. Plasma ANP fell significantly 10 min after LAP was normalized by constriction of the IVC but not when LAP was normalized by constriction of the PA, because PA constriction caused a significant rise in right atrial pressure that stimulated ANP secretion. The increases in plasma AVP and PRA after normalizing LAP by constriction of the PA were compared with the increases obtained during identical falls in MAP induced by constriction of the IVC alone, a maneuver that lowers LAP below control. The increases in plasma AVP in the two conditions were identical, indicating that the stimulation of left heart baroreceptors alone can account for the suppression of AVP secretion in response to unloading arterial baroreceptors. In contrast, there was a greater rise in PRA during hypotension caused by constriction of the IVC alone compared with the condition in which LAP was normalized but plasma ANP remained elevated. This suggests that increased left heart pressure inhibits renin secretion in response to arterial hypotension by reflex mechanisms and by increased plasma ANP concentration.

Pulsed lasers in particle detection and sizing.

We demonstrate the feasibility of using a pulsed copper vapor laser in particle detection and sizing, Despite the low-duty cycle of these lasers (0.025%), the forward scatter of light from 5-microm latex spheres has been detected.

Role of right heart receptors in the control of renin, vasopressin, and cortisol secretion in dogs.

We have reported that increased left heart pressure inhibits increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol during arterial hypotension. The goal of this study was to determine whether increases in right heart pressure also inhibited hormonal responses to hypotension. Seven dogs were chronically instrumented with inflatable cuffs around the ascending aorta (AA), the pulmonary artery (PA), and the thoracic inferior vena cava (IVC), as well as with catheters in both atria, the abdominal aorta, and vena cava. The IVC, the PA, and the AA cuffs were inflated on different days to cause step reductions in mean arterial pressure (MAP) of 5, 10, 20, and 30% below control MAP. Graded constriction of the AA caused large increases in left atrial pressure and plasma atrial natriuretic peptide (ANP), but had no effect on plasma AVP or cortisol and caused only a small increase in PRA at the maximal reduction of MAP. Constriction of the IVC reduced both atrial pressures and plasma ANP, but stimulated increases in PRA, AVP, and cortisol. Constriction of the PA increased right atrial pressure and plasma ANP and caused increases in plasma AVP and cortisol that were similar to responses during IVC constriction, but the PRA response was only half (P < 0.05). These results indicate that increasing pressure on the right side of the heart can attenuate the PRA response to hypotension, and suggest that the inhibition is mediated by the rise in plasma ANP.

Mechanism of drinking-induced inhibition of vasopressin secretion in dehydrated dogs.

Ingestion of water stimulates a powerful inhibitory input to secretion of arginine vasopressin (AVP) in many species. A previous study in dogs has suggested that the stimulus arises from activation of oropharyngeal receptors, but the nature of the stimulus is unknown. The objectives of this study were to determine if the taste, osmolality, or temperature of the solution ingested constituted an important element in the inhibitory mechanism and if these same attributes affected the volume ingested in response to 24 h of water deprivation in conscious dogs. Experiments consisted of a control period, a 6-min period of access to fluid, and a 60-min period after drinking, with blood samples taken frequently to assess changes in plasma AVP. Dogs were placed in a sling that allowed them to stand or lie supported with easy access to a bowl. The solutions were water at 20 and 38 degrees C; 0.9% NaCl at 20 and 38 degrees C; 1.8 and 2.7% NaCl at 20 degrees C; 5% glucose and mannitol and 10% mannitol at 20 degrees C; and liquified food at 20 degrees C. In the time-control experiment dogs were allowed to see but not drink water for 6 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of fluid intake in dogs following water deprivation.

Whereas water loss in land living animals occurs continuously, water intake takes place discontinuously. At the normal operating set point of plasma osmolality, urine is more concentrated than plasma due to secretion of vasopressin. Thus animals operate around a state of mild dehydration. As water loss occurs, the severity of dehydration and thirst increase in intensity and at some point water intake occurs. Sufficient water is consumed to return plasma osmolality to the normal operating set point. Food intake and water balance are interdependent as food provides the osmoles which determine obligatory renal solute excretion. When dry food with the same osmotic content was substituted for canned food (water content 74%), dogs increased water intake from 24.2 +/- 4.3 to 62.2 +/- 8.8 ml/kg. Urine output and urine osmolality were unchanged, as under conditions of normal hydration, near maximal urine concentration is achieved. Changing water intake is the only available variable to maintain water balance. During water deprivation, the major renal mechanism appears to be natriuresis. In rehydration, satiety mechanisms ensure appropriate water intake and renal sodium conservation restores sodium balance.

The importance of thirst in maintenance of fluid balance.

Plasma osmolality is maintained within very narrow limits by the control of water intake via thirst and water output via secretion of vasopressin. Osmoreceptors are situated in the brain, but on the blood side of the blood-brain barrier in a circumventricular organ. These regions are stimulated by an increase in plasma osmolality and form the most important input to cause thirst and drinking. Cardiopulmonary and arterial baroreceptors sensitive to blood volume and blood pressure also can be important, so hypovolaemic events such as haemorrhage can stimulate thirst. Both raised plasma osmolality and reduced blood volume contribute to thirst and vasopressin secretion following water deprivation. The importance of the nucleus medianus in the neural circuitary involved in integrating thirst should be emphasized. Mechanisms which stop drinking are different from those which initiate it, and oropharyngeal metering of the volume of fluid consumed provides the important input. There are a number of situations in humans where thirst thresholds and sensitivities are altered. The elderly have higher thirst thresholds and this can cause symptoms of dehydration. Increased drinking is seen in congestive heart failure, renal hypertension and certain cerebral lesions. Thirst thresholds are set at lower levels in pregnancy and in the luteal phase of the menstrual cycle and may contribute to fluid retention in these situations.

Mechanism of inhibition of renin response to hypotension by atrial natriuretic factor.

We have reported that infusion of atrial natriuretic factor (ANF) inhibited the rise in plasma renin activity (PRA) in response to constriction of the abdominal aorta to cause a reduction in renal perfusion pressure (RPP). To evaluate the effect of ANF on neural control of renin release, acute thoracic inferior vena caval constriction (TIVCC) was performed in conscious dogs to reduce arterial pressure by 25% of control and stimulate PRA by a reflex increase in renal nerve activity and a reduction in RPP. Propranolol was used to block neural stimulation of renin release. TIVCC caused significant increases in PRA, plasma aldosterone, arginine vasopressin (AVP), and adrenocorticotropic hormone (ACTH) concentrations. The increase in PRA was significantly reduced by the infusion of either ANF at 20 ng.kg-1.min-1 or propranolol. The combined infusion of ANF and propranolol produced an additive and complete inhibition of the renin response to TIVCC; therefore the effect of ANF is independent of neural stimulation of renin release. ANF at 20 ng.kg-1.min-1 also inhibited increases in aldosterone, AVP, and ACTH, but ANF at 5 ng.kg-1.min-1 only affected the aldosterone response to TIVCC. Therefore ANF inhibits angiotensin II-stimulated aldosterone synthesis and/or secretion at very low doses and at higher doses attenuates reflex increases in AVP and ACTH caused by hypotension.

Physiological doses of atrial peptide inhibit angiotensin II-stimulated aldosterone secretion.

The current study was designed to investigate the potential of atrial peptide to serve as a physiological regulator of aldosterone secretion. Conscious chronically instrumented dogs were given a constant intravenous infusion of either atrial peptide [ANP-(1-28); 5, 25, or 100 ng.kg-1.min-1] or vehicle (saline). Once steady-state conditions were achieved, angiotensin II was infused in a ramp design to stimulate aldosterone secretion (2.5-40 ng.kg-1.min-1). In the absence of atrial peptide, angiotensin II induced dose-dependent increases in plasma aldosterone concentration. In the presence of a 5-ng.kg-1.min-1 infusion of atrial peptide, the aldosterone response was reduced an average of 65 +/- 11%. When atrial peptide was infused at 25 and 100 ng.kg-1.min-1, the response was totally abolished. These results show that atrial peptide is a potent inhibitor of angiotensin II-stimulated aldosterone secretion. The results suggest that normal variations in plasma atrial peptide concentration can play an important role in the regulation of aldosterone secretion and fluid and electrolyte balance.

Role of renal sympathetic nerves in renin inhibition by elevated left atrial pressure.

We have reported that the renin response to systemic hypotension during a simultaneous increase in left atrial pressure (LAP) depends, in part, on intact renal nerves. Because efferent neural control of renin release is mediated by renal sympathetic nerves, we tested the hypothesis that withdrawal of renal sympathetic tone is an essential component of the inhibitory mechanism. In conscious dogs, the ascending aorta was partially constricted to produce a simultaneous decrease, of up to 30%, in renal perfusion pressure (RPP) and a rise in LAP. Sympathetic neural control of renin release was reversibly blocked with propranolol. Propranolol infusion did not affect the increases in LAP or atrial natriuretic factor (ANF) during ascending aortic constriction. There was no increase in renin (P greater than 0.1) during ascending aortic constriction, with or without propranolol infusion. Identical reductions in RPP during constriction of the abdominal aorta caused renin to rise (P less than 0.03). Therefore acute withdrawal of renal sympathetic tone is not necessary for the inhibition of the renin response to systemic hypotension by elevated LAP.

Atrial peptide potentiates renal responses to volume expansion in conscious dogs.

Experiments were performed to compare the renal responses to atrial peptide infusion in conscious dogs with normal and expanded extracellular fluid volumes to test the hypothesis that the renal responses to atrial peptide infusions are dependent on the prevailing fluid and electrolyte status in the animal. Atrial peptide-(99-126) was infused intravenously in doses of either 0, 5, 25, or 100 ng.kg-1.min-1 in conscious dogs prepared with chronic catheters in the femoral artery and vein and the urinary bladder. In dogs with normal extracellular fluid volume, atrial peptide caused small increases in urinary sodium excretion with the high physiological (25 ng.kg-1.min-1) and pharmacological (100 ng.kg-1.min-1) doses. Urine volume and potassium excretion were increased only at the highest pharmacological dose. In contrast, atrial peptide infusion in dogs that were volume expanded by infusion of hypertonic saline showed dramatic, dose-dependent increases in sodium excretion and urine flow with all doses tested. The low, physiological dose of atrial peptide (5 ng.kg-1.min-1) increased sodium excretion and urine flow rate in volume-expanded dogs more than the pharmacological dose in normal dogs (n = 4). These results demonstrate that the renal responses to atrial peptide infusion are potentiated in dogs that are volume expanded and suggest that under conditions where atrial peptide secretion would be enhanced, small changes in plasma atrial peptide concentration can have significant effects on renal function.

Physiological responses to low dose infusions of atrial peptide in conscious dogs.

Mongrel dogs prepared with chronic catheters in their femoral artery and vein and urinary bladder received 60 minute infusions of atrial peptide ranging from 5 to 100 ng/kg/min. Infusion of atrial peptides caused dose dependent increases in plasma atrial peptide concentration with doses of 25 ng/kg/min or less increasing plasma concentrations to levels observed in normal animals during stimulation of endogenous atrial peptide secretion. Atrial peptide infusion at doses of 10 ng/kg/min and above caused significant decreases in mean arterial pressure which were not accompanied by statistically significant changes in heart rate. Atrial peptide infusion at doses of 25 ng/kg/min and above increased urinary sodium excretion and urine flow rate. Atrial peptide infusion was without effect on plasma vasopressin, ACTH and corticosterone concentrations. However, atrial peptide infusion resulted in dose dependent decreases in plasma aldosterone concentration and plasma renin activity, but the decreases were only significant with the high physiologic (25 ng/kg/min) and pharmacologic doses (50 & 100 ng/kg/min). These data show that atrial peptide infusions in conscious dogs have minimal effects when infused in small doses that mimic endogenous atrial peptide release. At higher doses, significant effects on the cardiovascular, renal and endocrine systems can be observed but their physiological significance is unclear.

Endocrine components of body fluid homeostasis.

1. Linear relationships between plasma osmolality and thirst and vasopressin secretion are described in conscious dogs. 2. During water deprivation, natriuresis occurs which ameliorates the rise in plasma osmolality. 3. Increases in plasma osmolality prevent the stimulation of aldosterone secretion by angiotensin II.

Drinking, oropharyngeal signals, and inhibition of vasopressin secretion in dogs.

Ingestion of water leads to a rapid fall in plasma levels of vasopressin in 24-h water-deprived dogs. The rapid inhibition of vasopressin secretion is not due to absorption of water and dilution of plasma nor is it due to gastric distension. Blood pressure rises sharply during drinking, and this may provide the afferent signal leading to inhibition of vasopressin secretion. Other possibilities include a generalized increase in oropharyngeal motor activity or simply the sight of water. To test these hypotheses, 24-h water-deprived dogs were given either phenylephrine, to mimic the rise in blood pressure observed during drinking, offered canned meat, to induce oropharyngeal motor activity and swallowing, or presented with a bowl of water that was placed just out of reach. Administration of phenylephrine, ingestion of food, and the presence of water all caused increases in blood pressure, which were similar to the rise in blood pressure during drinking. However, none of these paradigms caused a fall in plasma vasopressin. In contrast, ingestion of water consistently led to a significant fall in plasma vasopressin, which was detectable within 3 min of drinking and well before changes in plasma osmolality. Therefore we conclude that the mechanism by which ingestion of water causes rapid inhibition of vasopressin secretion in dehydrated dogs cannot be dependent on a rise in blood pressure, a nonspecific increase in oropharyngeal motor activity, or the presence of water.

Atrial natriuretic peptide blocks renin response to renal hypotension.

We have reported that the renin response to systemic hypotension is inhibited in the presence of elevated atrial pressure and that elevations in atrial pressure of similar or larger magnitude cause graded increases in plasma atrial natriuretic peptide (ANP). Therefore we tested the hypothesis that comparable increments in plasma ANP can inhibit renal hypotension-induced increases in plasma renin activity (PRA) in conscious dogs. Renal perfusion pressure was controlled using cuffs implanted around the abdominal aorta just above the renal arteries. Reducing renal perfusion pressure by 10 or 30% of control caused graded increases in PRA (P less than 0.01). Infusion of 1-28 rat ANP (5 ng X kg-1 X min-1), which increased plasma ANP by 34.8 +/- 7.5 (SE) pg/ml, eliminated increases in PRA in response to a 10% reduction in renal perfusion pressure and markedly inhibited the response to a 30% pressure reduction (P less than 0.01). These results indicate that increments in plasma ANP which reproduce endogenous release inhibit renal hypotension-induced stimulation of PRA. Furthermore, the results provide an explanation for the inhibition of the renin response to renal hypotension during elevated atrial pressure.

Increased synthesis and release of atrial peptide during DOCA escape in conscious dogs.

The escape from the sodium-retaining effects of prolonged mineralocorticoid treatment in animals and humans was first noted over 40 yr ago, but despite intense study the mechanisms responsible for the escape phenomenon have not been identified. Putative "natriuretic hormones" have been proposed to account for the escape phenomenon. To determine whether atrial natriuretic peptides (ANP) could participate in the escape phenomenon, the mineralocorticoid deoxycorticosterone acetate (DOCA) was administered to conscious dogs for 14 days. Escape was accompanied by a doubling of plasma ANP concentration and four- to sevenfold increases in cardiac ANP messenger RNA. There were also significant increases in mean arterial blood pressure during the last 8 days of DOCA treatment. Thus increases in the synthesis and secretion of ANP and increases in atrial pressure may represent mechanisms that contribute to the escape from mineralocorticoid-induced sodium retention.

Increased right or left atrial pressure stimulates release of atrial natriuretic peptides in conscious dogs.

To compare release of immunoreactive atrial natriuretic peptides (iANP) caused by distention of the right and left atria, dogs were prepared with occluding cuffs around either the ascending aorta (n = 5) or the pulmonary artery (n = 4). Graded inflation of the ascending aortic cuff for 60 min caused increments in left atrial pressure (LAP) but no change or a decrease in right atrial pressure (RAP). Plasma iANP increased significantly (P less than 0.01) in response to increases in LAP as small as 2.9 +/- 0.4 mmHg. There was a significant correlation between the increment in LAP and the rise in plasma iANP (r = 0.64, n = 25, P less than 0.01). Graded inflation of the pulmonary artery cuff caused increments in RAP and a fall in LAP. Plasma iANP increased significantly (P less than 0.01) in response to increases in RAP as small as 2.8 +/- 1.1 mmHg. Also, there was a significant correlation between the increments in RAP and the rise in plasma iANP (r = 0.69, n = 20, P less than 0.01). These results indicate that physiologic increases in either RAP or LAP is sufficient to cause increased plasma levels of iANP in conscious dogs.