David J. Ramsay

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.

Role of Volume and Osmolality in the Control of Plasma Vasopressin in Dehydrated Dogs

Plasma vasopressin concentrations (pAVP) are elevated during dehydration due to alterations in extracellular fluid (ECF) volume and tonicity. The contributions of the reduction in volume and increase in plasma osmolality to the rise in pAVP were assessed in 6 dogs with bilateral carotid loops following 24 h of fluid, but not food, deprivation. Dehydration significantly (p less than 0.05) increased plasma osmolality from 297 +/- 1 to 315 +/- 2 mosm/kg), decreased body weight from 20.8 +/- 1.2 to 20.3 +/- 1.2 kg, and elevated pAVP from 1.4 +/- 0.2 to 5.3 +/- 0.6 pg/ml. The effect of extracellular fluid volume reduction was tested by reexpanding this compartment in dehydrated dogs with 0.15 M NaCl. Plasma vasopressin concentration was significantly reduced by 1.3 +/- 0.2 pg/ml (33 +/- 4%) and plasma osmolality unchanged following volume replacement. The contribution of the increase in plasma osmolality was assessed by bilateral intracarotid infusions of water at 0.6 ml/min/artery which lowered jugular venous plasma osmolality to euhydrated values (296 +/- 4 mosm/kg), but did not significantly reduce systemic plasma osmolality. Plasma vasopressin levels were significantly reduced 3.2 +/- 1.1 pg/ml (70 +/- 5%). Thus, following 24 h of fluid deprivation in dogs, the rise in pAVP is due to changes in both ECF volume and tonicity. The increase in tonicity plays a greater role in the elevation of pAVP, than the reduction in volume.

CNS regulation of salt and water intake.

The brain has evolved a number of mechanisms to maintain body fluid balance. They include the sensation of thirst, which stimulates water intake, the secretion of vasopressin, which helps prevent water loss, and the secretion of aldosterone, which helps prevent sodium depletion. In the research described here, all three mechanisms are shown to be mediated by the actions of angiotensin on the brain.

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.

Mechanism of the dipsogenic action of tetradecapeptide renin substrate

The mechanism of the dipsogenic action of synthetic tetradecapeptide renin substrate (TDP) was studied in rats with chronically implanted lateral ventricular cannulae. All hormones and drugs were injected via the ventricular cannulae. The dipsogenic action of TDP was unaffected by the renin inhibitor pepstatin but was markedly reduced by the angiotensin converting enzyme inhibitor SQ 20881. Homogenates of rat brain readily formed angiotensin II from TDP in vitro and this was likewise unaffected by pepstatin but was reduced or abolished by SQ 20881 or by chelating agents. Natural renin substrate did not cause drinking and did not generate angiotensin II when incubated with brain homogenates. These results demonstrate that rat brain converting enzyme can generate angiotensin II from TDP and that this effect is responsible for the dipsogenic action of TDP.

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.

EFFECT OF OSMOTIC STIMULI ON THE CONCENTRATION OF VASOPRESSIN IN JUGULAR AND PERIPHERAL VENOUS PLASMA

Publisher Summary The relation between the rate of secretion of vasopressin and the osmolality of the body fluids is a basic element of the extracellular fluid homeostasis. The chapter presents experiments conducted on conscious, euhydrated dogs, which evaluate the effect of short, bilateral, and intracarotid infusions of hypertonic saline on the concentrations of vasopressin in jugular and systemic plasma. The results show that (1) infusions of hypertonic saline bilaterally into the common carotid arteries are associated with an increase in the concentration of vasopressin in plasma, (2) intravenous administration of identical, hypertonic solutions are ineffective - or at least much less effective - in eliciting the release of vasopressin, and (3) the difference between the concentration of vasopressin in jugular venous plasma and the concentration in venous plasma from a hind leg is small and statistically demonstrable only in some of the animals. The mechanisms responsible for the control of the secretion of vasopressin normally maintain a delicate balance sensitive to stimuli, which are part of homeostatic systems and to perturbations, which a priori would have appeared less likely to influence the secretion of this hormone..