T. N. Thrasher

Deficits in Drinking and Vasopressin Secretion after Lesions of the Nucleus medianus

The effects of ablation of the nucleus medianus on drinking and vasopressin secretion were studied in male Long-Evans rats. The amount of water drunk in 1 h was assessed after subcutaneous injection of 5.8% NaCl (13.34 mosm/kg) or of angiotensin II (1.5 mg/kg). In a separate test with no water available, plasma vasopressin was measured 15 min after the above dose hypertonic saline. Ablation of the nucleus medianus, or the dorsal and anterior portions of the nucleus medianus, blocked drinking to hypertonic saline or angiotensin II and attenuated the vasopressin response to hyperosmolality. Animals with septal or diagonal band lesions showed responses comparable to sham-operated rats. These results indicate that a neural pathway important for fluid balance passes through, or terminates in, the nucleus medianus.

Role for the subfornical organ in vasopressin release

The effect of subfornical organ (SFO) lesions on plasma vasopressin and drinking was tested in rats given either of two stimuli: subcutaneous injection of hypertonic saline or injection of a single dose of angiotensin II (AII) into the dorsal third cerebral ventricle. Drinking in response to hypertonicity was significantly attenuated, whereas AII-induced drinking was unaffected by the lesions. In contrast, SFO lesions were associated with significantly reduced vasopressin responses following either of these potent stimuli to vasopressin secretion. Partial lesions that damaged structures adjoining the SFO (fornix or septum) had no significant effects. These results demonstrate that, in rats, the SFO is in some way necessary for vasopressin responses to both AII and hypertonicity.

Baroreceptor Regulation of Vasopressin and Renin Secretion: Low-Pressure versus High-Pressure Receptors

The high-pressure or arterial baroreceptors and low-pressure or atrial receptors are believed to participate in the reflex control of arginine vasopressin (AVP) and renin secretion. The current concept of the control system is that at normal blood volume and pressure, afferent impulses from the receptors tonically inhibit central mechanisms controlling secretion of AVP and renin. Thus, a reduction in blood volume or pressure causes a decrease in receptor activity and a reflex increase in hormone secretion; conversely an increase in blood volume causes the opposite sequence of events. Furthermore, it is widely believed that cardiac atrial receptors are more important than arterial baroreceptors in the reflex control of AVP and renin secretion. Evidence presented in this review challenges the traditional view that cardiac receptors are importantly involved in the reflex control of AVP secretion. Recent evidence indicates that plasma AVP does not increase during progressive hypovolemia until volume loss causes a frank fall in arterial pressure. Furthermore, the evidence suggests that it is the sudden unloading of arterial baroreceptors that triggers the surge in AVP secretion and not signals from cardiac receptors. There is also very little evidence that increasing the load on cardiac receptors inhibits AVP secretion. In contrast, there is considerable evidence that renal sympathetic nerve activity, and hence reflex control of renin secretion, is tightly and inversely coupled to changes in blood volume. Furthermore, the evidence supports the concept that atrial receptors are the mediators of the fine reflex control of renin secretion in response to changes in blood volume.

Lesions of the Subfornical Organ Block Angiotensin-Induced Drinking in the Dog

The role of the subfornical organ (SFO) in drinking caused by cellular dehydration and angiotensin was examined in the dog. Drinking responses to intravenous administration of angiotensin and to hypertonic NaCl were compared before and after electrolytic ablation of the SFO. After destruction of the SFO, drinking in response to angiotensin was 0.5 +/- 0.3 ml/kg compared to 11.9 +/- 3.7 ml/kg prior to lesioning. Drinking in response to hypertonic NaCl was not affected by lesioning the SFO (12.6 +/- 6.6 ml/kg before vs. 13.4 +/- 5.4 ml/kg after the lesion). Lesions superior or lateral to the SFO did not affect drinking in response to either angiotensin or hypertonic NaCl. These data show that the SFO is essential for drinking in response to blood-borne angiotensin but not to the stimulus of cellular dehydration in the dog.

The Organum Vasculosum Laminae Terminalis: A Critical Area for Osmoreception

Publisher Summary The volume and composition of the body fluids is maintained by coordinated control of water intake by thirst mechanisms and water output via vasopressin secretion. This chapter describes and presents evidence in favor of the organum vasculosum laminae terminalis (OVLT) as site of osmoreception (both osmotic and volaemic regulation of water balance). Evidence presented in the chapter demonstrates that the osmoreceptors behave as if they were located in an area of the brain lacking the blood-brain barrier and that this area is likely to be in the anterior hypothalamus. Although, there is electrophysiological evidence that cells elsewhere in the brain, such as the supraoptic nucleus, show osmosensitivity, their capacity to respond to reasonable osmotic challenges is in question. Animals with discrete lesions of the OVLT have greatly diminished responses to osmotic stimuli and abolition of these responses over reasonable physiological range, whereas the identity of the osmoreceptors remains elusive; their anatomical home, the OVLT, is more certain.

Arterial baroreceptors control blood pressure and vasopressin responses to hemorrhage in conscious dogs

The goal of this study was to determine the role of arterial baroreceptors in the reflex control of arginine vasopressin (AVP), renin, and cortisol secretion in response to a 30-ml/kg hemorrhage in conscious dogs. The hormonal responses were measured in six dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD + CD. In the intact condition, mean arterial pressure (MAP) was maintained at control levels until blood loss reached 20 ml/kg and the absolute magnitude of the fall at 30 ml/kg was 35 ± 10 mmHg. Similar responses were obtained during acute CD. In contrast, MAP fell earlier (at 5 ml/kg, P < 0.05) and to much lower levels in both the SAD and SAD + CD conditions. The individual slopes relating systolic pressure to plasma AVP, renin activity (PRA), and cortisol were used to compare the treatment effects using a 2 × 2 factorial analysis. There was a significant ( P < 0.01) effect of SAD on the slope relating AVP to systolic pressure but no effect of CD and no SAD × CD interaction. In contrast, there was no effect of either SAD or CD on the relationship between PRA or plasma cortisol and systolic pressure. These results indicate that maintenance of blood pressure and the normal pattern of AVP secretion during hemorrhage depend on intact arterial baroreceptor reflexes.The goal of this study was to determine the role of arterial baroreceptors in the reflex control of arginine vasopressin (AVP), renin, and cortisol secretion in response to a 30-ml/kg hemorrhage in conscious dogs. The hormonal responses were measured in six dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD + CD. In the intact condition, mean arterial pressure (MAP) was maintained at control levels until blood loss reached 20 ml/kg and the absolute magnitude of the fall at 30 ml/kg was 35 +/- 10 mmHg. Similar responses were obtained during acute CD. In contrast, MAP fell earlier (at 5 ml/kg, P < 0.05) and to much lower levels in both the SAD and SAD + CD conditions. The individual slopes relating systolic pressure to plasma AVP, renin activity (PRA), and cortisol were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating AVP to systolic pressure but no effect of CD and no SAD x CD interaction. In contrast, there was no effect of either SAD or CD on the relationship between PRA or plasma cortisol and systolic pressure. These results indicate that maintenance of blood pressure and the normal pattern of AVP secretion during hemorrhage depend on intact arterial baroreceptor reflexes.

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.

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.

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.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.