Secretion In Conscious Dogs Research Articles

Effects of an antral mucosectomy, L-364,718 and atropine on cephalic phase of gastric and pancreatic secretion in dogs

The purpose of this study was to determine the role of gastrin and cholecystokinin in the cephalic phase of gastrin release and gastric and pancreatic secretion in conscious dogs. Sham feeding in intact dogs increased gastric acid output to about 65% of histamine maximum and pancreatic protein to 23% of caerulein maximum. Significant increases in plasma gastrin and pancreatic polypeptide but not cholecystokinin occurred. Similar effects were obtained using insulin hypoglycemia or 2-deoxy-D-glucose glucocytopemia. Atropine eliminated gastric acid response to sham feeding, insulin, or 2-deoxy-D-glucose, significantly reduced the pancreatic protein response by about 60%, and abolished plasma pancreatic polypeptide but not plasma gastrin. Blocking of cholecystokinin receptors by L-364,715 did not affect gastric or pancreatic secretory responses to sham feeding, insulin, or 2-deoxy-D-glucose and failed to influence the accompanying increments in plasma gastrin and pancreatic polypeptide. In antral-mucosectomized dogs, sham feeding-induced acid output reached only 17% of histamine maximum but the increase in pancreatic protein output was similar to that in intact dogs. In these animals, background stimulation with G17I (62 pmol/kg per h) potentiated the gastric acid response to sham feeding but had little effect on pancreatic protein output. This study provides evidence that unlike gastric acid, the pancreatic protein response to physiological or pharmacological cephalic stimulation does not depend on vagally released gastrin but probably on direct vagal stimulation of the pancreas.

Effects of Cholera Toxin on Small Intestinal Motor Activity in the Fasted State

We sought to determine the effect of cholera toxin on small intestinal motor activity in the fasted state and relate it to secretion in conscious dogs. Motor activity was recorded by strain gauge force transducers and secretion was measured by diverting it to the outside through a two‐way cannula. Inoculation of the study segment with cholera toxin resulted in a 10‐fold increase in fluid output by 120 minutes postinjection. At the same time that fluid output increased Significantly changes in fasting motor activity occurred. The cycle length of the migrating motor complex was significantly reduced, the percentage of phase II activity was significantly increased, and migrating clustered contractions were inhibited. Perfusion of the study segment by a nonabsorbable electrolyte solution at a rate similar to the rate of secretion induced by cholera toxin did not change the cycle length of migrating motor complexes, but the percentage of phase II activity was significantly increased as with cholera toxin, and migrating clustered contractions were inhibited. The reduction in the cycle length of migrating motor complexes seems to be a direct effect of cholera toxin on the gut wall while the increase in percentage of phase II activity and inhibition of migrating clustered contractions appear to be indirect effects due to fluid accumulation.

Feedback control of vasopressin and corticotrophin secretion in conscious dogs: effect of hypertonic saline

Glucocorticoids are known to inhibit the ACTH response to a variety of stimuli. It has been suggested that vasopressin secretion is also inhibited by glucocorticoid negative feedback. The purpose of this study was to (1) determine the ACTH response to hypertonic saline and its sensitivity to glucocorticoid negative feedback and (2) to determine whether physiological elevations of plasma cortisol inhibit subsequent vasopressin responses to hypertonic saline. Five mongrel dogs (15-18 kg) were prepared with chronic arterial and venous catheters and studied while conscious. Ten experiments were performed on each dog in a randomized design separated by at least 5 days. Each experiment consisted of a pretreatment period (from -60 to -30 min except for dexamethasone administration) during which a glucocorticoid feedback signal was applied and a stimulus period (from 0 to 30 min) during which hypertonic saline was infused. The pretreatment and stimulus periods were separated by 30 min. Pretreatments were as follows: isotonic saline (control), half-maximal and maximal cortisol infusion (5.5 or 11 nmol/kg per min), ACTH(1-24) infusion (6.8 pmol/kg per min) which produces increases in endogenous cortisol, and dexamethasone (1.5 mg i.m.) given at 17.00 h the day before experimentation. Stimuli were as follows: hypertonic saline was infused at 0.2 or 0.4 mmol/kg per min which increased plasma sodium by about 6 or 12 mmol/l respectively. NaCl infusion at 0.2 mmol/kg per min had no effect on plasma ACTH or cortisol except when subsequent to ACTH(1-24) pretreatment when plasma ACTH actually increased to 41.4 +/- 2.9 pmol/l in response to hypertonic saline.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between blood gastrin levels and gastric secretion in conscious dogs.

1. In conscious dogs with gastric fistulae and Heidenhain pouches, acid and pepsin secretion, immunoreactive plasma pancreatic polypeptide (PP) and gastrin were measured following intravenously administered pentagastrin, cholinomimetics, and intragastric administration of milk. 2. Pentagastrin did not raise endogenous plasma gastrin. There was a significant positive dose-response relationship between pentagastrin and acid and fistula pepsin secretions, but not between plasma gastrin of endogenous origin and gastric secretion. 3. Carbachol raised plasma gastrin immunoreactivity; but in no instance was there a significant relationship between gastric secretion and plasma gastrin immunoreactivity. Gastric acid secretion faded, but plasma gastrin concentrations did not. 4. PP plasma immunoreactivity was elevated by methacholine and carbachol. Its levels correlated significantly with gastric acid secretion. Pentagastrin did not raise PP and its levels did not, therefore, correlate with gastric acid secretion. 5. Intragastric milk raised plasma gastrin immunoreactivity, but the acid secretion per pg of plasma gastrin was much smaller than with the cholinomimetics. Ganglionic blocking agents depressed both plasma gastrin and acid and pepsin secretion. 6. The results suggest that cholinomimetics sensitize parietal cells to the stimulating action of gastrin.

The effect of cholecystokinin-related peptides on periodic pancreatic secretion in fasting dogs.

1. The effect of cholecystokinin octapeptide (CCK-8) and pentagastrin on periodic pancreatic secretion was studied in fasting conscious dogs. 2. Both CCK-8 and pentagastrin, in small doses, prolonged the interval of periodic pancreatic secretion. Periodicity was disrupted by large doses of CCK-8 and pentagastrin. 3. CCK-8, at the dose which did not disrupt the cycle, raised the peak and the valley-to-valley means, but not the valley mean, of protein secretion in one cycle. Except at large doses, pentagastrin failed to increase the peak and valley mean, but increased mean, valley-to-valley protein secretion. Large doses of both pentagastrin and CCK-8 increased protein secretion at the valley. 4. The peak of periodic pancreatic protein secretion was about half the observed maximum protein response to CCK-8. 5. Atropine reduced pancreatic fluid and protein responses to small doses of CCK-8 to the levels of valleys. At large doses, however, both responses were augmented by atropine. Hexamethonium reduced the responses to any dose of CCK-8 to valley levels or less. Volume and protein responses to pentagastrin following atropine or hexamethonium were of similar magnitude to those at valleys. 6. It is concluded that CCK-8 and pentagastrin stimulate pancreatic enzyme secretion directly by acting on acinar cells and indirectly by modifying cholinergic ganglionic activities which control periodic secretion in conscious dogs.

Effects of peptide YY on dog and rat pancreatic secretion in vivo and in vitro

The action of peptide YY (PYY) on exocrine pancreatic secretion in dogs and rats was compared in in vivo and in vitro studies. PYY infused i.v. in the physiological dose range (125-1000 pmol/kg.h) reduced in a dose-dependent manner the pancreatic protein response to caerulein and suppressed basal and meat feeding or duodenal oleate-induced pancreatic secretion in conscious dogs. Both meat feeding and duodenal oleate caused significant elevation of plasma PYY levels and these showed several-fold increase during infusion of exogenous PYY (500 pmol/kg.h) inducing significant inhibition of the postprandial or oleate-stimulated pancreatic secretion. PYY in a dose range of 2.5-40 nmol/kg.h also inhibited the response to caerulein in conscious rats but failed to prevent the increment in the postprandial protein secretion in this species. PYY added in various concentrations (10(-11)-10(-6) M) to the incubation medium of the isolated dog and rat pancreatic acini failed to affect basal or caerulein- and urecholine-stimulated amylase release. This study shows that PYY is an effective inhibitor of the pancreatic secretion in vivo but not in vitro suggesting that the inhibition is mediated by an indirect mechanism.

Cephalic phase response of pancreatic exocrine secretion in conscious dogs.

The effects of three taste solutions on the cephalic phase of pancreatic secretion were studied in conscious dogs. Male beagle dogs weighing 9-11 kg were prepared with gastric and duodenal fistulas. Gustatory receptors were stimulated for 5 min with 100 ml of 0.5% agar solutions containing 0.05, 0.12, and 0.3 M of either sodium chloride, sucrose, or monosodium glutamate (MSG). Pancreatic juice was collected every 5 min before and after stimulation, and volume flow and protein output were measured. Pancreatic secretory responses were found to vary with the type of taste stimulus. Sucrose was a better stimulus than MSG for both protein output and volume flow. Taste stimulation with sodium chloride produced a lower pancreatic response than those with sucrose or MSG.

Role of secretin and CCK in the stimulation of pancreatic secretion in conscious dogs. Effects of atropine and somatostatin.

The role of gut hormones, such as secretin and CCK, in the stimulation of pancreatic secretion by duodenal HCl or oleate and by meat feeding has been studied in conscious dogs before and after pretreatment with atropine and somatostatin. Plasma hormones were measured by specific and sensitive radioimmunoassays. Duodenal perfusion with HCl and oleate stimulated dose-dependently pancreatic HCO3 and protein secretion and raised plasma levels of secretin and CCK, respectively. Atropine reduced significantly both HCO3 and protein secretion but did not affect plasma secretin and CCK levels in these studies. Both exocrine pancreatic secretion and plasma secretin and CCK levels were suppressed by somatostatin. Meat feeding caused a marked pancreatic HCO3 and protein secretion accompanied by a significant increase in plasma secretin and CCK which seem to play an important role in the postprandial pancreatic stimulation. Both atropine and somatostatin reduced the pancreatic secretion induced by exogenous hormones but only somatostatin, but not atropine, significantly decreased plasma secretin and CCK responses to intestinal stimulants. We conclude that both atropine and somatostatin reduce the pancreatic responses to duodenal HCl or oleate or to meat feeding but only somatostatin is capable of suppressing the release of secretin and CCK.

Peptide YY interacts with secretin and duodenal acidification to inhibit gastric acid secretion.

Previous studies have indicated that plasma levels of peptide YY (PYY) increase significantly after a meal. The purpose of this study was to characterize the interaction of PYY and secretin in the inhibition of gastric acid secretion, and to determine whether PYY can influence acid-induced inhibition of gastric acid secretion in conscious dogs. I.v. administration of PYY at 200 pmol/kg/h inhibited pentagastrin (1 microgram/kg/h)-stimulated gastric acid output (P less than 0.05). PYY further augmented i.v. secretin-induced inhibition of pentagastrin-stimulated gastric acid output by 32 +/- 7%, and intraduodenal hydrochloric acid-induced inhibition of pentagastrin-stimulated gastric acid output by 40 +/- 12%. The mean integrated release of secretin response to duodenal acidification (3.9 +/- 1.0 ng-[0-60] min/ml) was not affected by PYY (3.3 +/- 0.9 ng-[0-60] min/ml). The present study demonstrates that PYY can interact with secretin and duodenal acidification in an additive fashion to inhibit pentagastrin-stimulated gastric acid secretion. Our results suggest that several hormones that are released postprandially can interact with each other to inhibit gastric acid secretion.

Peripheral opioid receptors mediate gastrointestinal secretory and motor effects of dermorphin N-terminal tetrapeptide (NTT) in the dog

Dermorphin N-terminal-tetrapeptide-amide (NTT) increased both basal and pentagastrin- or histamine-induced secretion in conscious dogs chronically implanted with both gastric fistulae and heidenhain pouches. These excitatory effects were significantly prevented by the opioid receptor antagonists naloxone and N-methyl-levallorphan-methanesulphonate. In conscious dogs fitted with electrodes and strain-gauges in different parts of gastrointestinal tract, a premature phase III of the migrating myoelectric complex (MMC) in the duodeno-jejunum was triggered by NTT, while the activity of the antrum was not significantly modified. Further, the peptide enhanced the contractile activity of both proximal and distal portions of the colon, including a long-lasting period of increased muscle tone on the distal colon. Either naloxone or N-methyl-levallorphan-methanesulphonate completely prevented motor effects of NTT on gastrointestinal tract. It is concluded that NTT displays significant opiate-like activity on gastric acid secretion and intestinal motility of the dog by activating peripheral μ opioid receptors.

Gastrin is not a physiological regulator of pancreatic exocrine secretion in the dog.

The role of gastrin as a regulator of exocrine pancreatic secretion has not been proven adequately. In the present study we therefore compared the relative molar potencies of sulfated and unsulfated gastrin 17 with structurally related CCK peptides (synthetic CCK-8 and natural porcine CCK-33) in stimulating exocrine pancreatic secretion in conscious dogs. Dose response curves were constructed for pancreatic and gastric acid secretion. Plasma gastrin levels after exogenous gastrin 17-I and -II were compared with postprandial gastrin concentrations (meal: ground beef 20 g/kg body wt). The molar potency estimates calculated with synthetic CCK8 as standard (potency = 1.00) for pancreatic protein secretion were natural porcine 50% pure CCK-33 1.60, gastrin 17-I 0.12, and gastrin 17-II 0.16. All four peptides induced a dose-dependent increase in pancreatic bicarbonate output. However, the blood concentrations needed to stimulate pancreatic secretion were above the postprandial gastrin levels. Our data indicate that both gastrin 17 peptides are not physiological regulators of pancreatic enzyme secretion in dogs.

Beta-Adrenergic Inhibition of Pancreatic Secretion in Dogs

Terbutaline, a beta-adrenergic agonist, administered subcutaneously inhibits pancreatic exocrine secretion. We studied the effects of intravenous terbutaline and propranolol on cholecystokinin-stimulated pancreatic secretion in conscious dogs. Terbutaline inhibited pancreatic juice volume, bicarbonate concentration, bicarbonate output and protein output, but had no effect on protein concentration. Propranolol blocked this inhibition and had no effect on the response to cholecystokinin. These observations suggest that (1) terbutaline inhibits pancreatic secretion by a beta-adrenergic mechanism and (2) the primary effect of terbutaline on canine exocrine pancreas is inhibition of water and bicarbonate secretion.

Inhibition of gastric acid secretion by brain peptides in the dog: Role of the autonomic nervous system and gastrin

We have studied the effects of 30 peptides administered intracerebroventricularly on basal and pentagastrin-stimulated (8 μg/kg s.c.) gastric acid secretion in conscious dogs. None of the peptides significantly increased basal gastric acid secretion. Twelve peptides (2 nmol/kg) significantly (p < 0.01) decreased the pentagastrin-stimulated 2-h acid output (percentage inhibition in parentheses): human calcitonin (CT) (36%), neurotensin (NT) (52%), rat corticotropin-releasing factor (CRF) (59%), human calcitonin gene-related peptide (CGRP) (59%), ovine CRF (66%), β-endorphin (β-End) (80%), urotensin-I (81%), rat CT (81%), porcine gastrin-releasing peptide (GRP) (83%), sauvagine (Svg) (85%), rat CGRP (87%), and bombesin (Bom) (95%). Blockade of the autonomic nervous system with chlorisondamine abolished the gastric inhibitory action induced by CRF, β-End, CT, and NT, but not by CGRP and Bom (1 nmol/kg each). Corticotropin-releasing factor, βEnd, CT, NT, CGRP, and Bom significantly inhibited gastric acid secretion stimulated by an intragastric 8% peptone meal for 2 h. None of these six peptides significantly altered plasma gastrin concentrations in response to the peptone meal as compared with control experiments. A rise of plasma concentrations of gastrin, CT, CRF, and CGRP could not be detected by radioimmunoassay in animals after intracerebroventricular administration of these four peptides. The results of this study indicate that CT, CGRP, NT, β-End, and peptides of the CRF and Bom families act within the brain to inhibit pentagastrinand meal-stimulated gastric acid secretion in conscious dogs. None of the 30 peptides administered intracerebroventricularly increased basal gastric acid secretion in the dog. Inhibition of gastric acid secretion induced by CRF, β-End, CT, and NT, but not by CGRP and Bom is mediated by the autonomic nervous system. Gastrin does not appear to play a role in gastric acid inhibition induced by the six brain peptides studied.

CNS actions of calcitonin gene-related peptide on gastric acid secretion in conscious dogs

To determine the mechanisms of action of calcitonin gene-related peptide (CGRP) in inhibiting gastric acid secretion, we studied awake male beagle dogs fitted with a chronic intracerebroventricular cannula and a gastric fistula. Synthetic rat CGRP (10 pmol/kg to 10 nmol/kg) given intracerebroventricularly or intravenously significantly inhibited pentagastrin-stimulated gastric acid secretion. CGRP (1 nmol/kg) given intracerebroventricularly decreased acid secretion stimulated by 2-deoxy-D-glucose but not by histamine. CGRP-(1-14), [Tyr23]CGRP-(23-37), and [acetamidomethyl-Cys2,7]CGRP, the linear peptide molecule devoid of the disulfide bridge, did not affect gastric secretion. Ganglionic blockade with chlorisondamine, a vasopressin antagonist, naloxone, and truncal vagotomy did not abolish the gastric inhibitory action of CGRP given intracerebroventricularly. CGRP administered intracerebroventricularly and intravenously decreased gastric acid secretion, but not plasma gastrin concentrations stimulated by an 8% peptone meal. It is concluded that CGRP given intracerebroventricularly or intravenously inhibits gastric acid secretion in conscious dogs; the intact molecule appears to be necessary for biological activity; and inhibition of gastric acid secretion by CGRP in the dog is not mediated by the autonomic nervous system or vasopressin-, opiate-, or gastrin-dependent pathways.

Role of the renin-angiotensin system in the control of vasopressin secretion in conscious dogs.

The present studies were designed to evaluate the physiological significance of angiotensin II in the control of vasopressin secretion in conscious dogs. They demonstrated that exogenous angiotensin II (10 ng/kg per min) increased vasopressin secretion more when the pressor effect of angiotensin II was abolished. The fact that endogenous angiotensin II levels are normally increased without an increase in arterial pressure suggests that angiotensin II may play a greater role in the control of vasopressin secretion than was previously thought. The present study also evaluated the role of endogenous angiotensin II in the control of vasopressin secretion during sodium depletion, a state in which angiotensin II levels are elevated. Intracarotid infusion of a low dose of the angiotensin II antagonist, saralasin, decreased plasma vasopressin concentration, suggesting that endogenous angiotensin II acts in an area of the brain perfused by the carotid arteries to stimulate vasopressin secretion in sodium-deprived dogs. Finally, the present experiments evaluated the role of angiotensin II in baroreceptor reflex control of vasopressin secretion. Baroreflex function was assessed by examining the relationship between the change in blood pressure and the log of the change in vasopressin secretion over a range of blood pressure levels. Exogenous angiotensin II (10 ng/kg per min) altered baroreflex function by causing a shift of this relationship to a higher pressure level in sodium-replete dogs. In sodium-depleted dogs, inhibition of the renin-angiotensin system with saralasin or captopril produced an opposite shift. These results suggest that endogenous angiotensin II may be necessary for the maintenance of normal baroreflex control of vasopressin secretion during sodium depletion. Collectively, these results support the hypothesis that endogenous angiotensin II plays a role in the control of vasopressin secretion.

Effect of somatostatin on histamine-stimulated gastric acid and pepsin secretion in dogs.

The purpose of the present study was to evaluate the effect of somatostatin on gastric acid secretion and pepsin secretion in conscious dogs with gastric fistula. Infusion of histamine stimulated dose-dependently the acid secretion, whereas pepsin secretion was decreased by the high doses of histamine. Somatostatin inhibited dose-dependently the stimulated acid secretion but only with a maximum of 40%. The pepsin secretion was inhibited by somatostatin dose-dependently and with a higher potency. The acid inhibition was of a competitive type and prostaglandin-independent.

Role of the vasoconstrictor and antidiuretic activities of vasopressin in inhibition of renin secretion in conscious dogs.

The nature of the activity of vasopressin that is responsible for the inhibition of renin secretion was studied in normally hydrated conscious dogs using intravenous infusions of vasopressin and analogues of vasopressin with selective antidiuretic and vasoconstrictor activity. Vasopressin (1.0 ng . kg-1 . min-1) increased mean arterial pressure (MAP) from 106 +/- 2 to 115 +/- 3 mmHg (P less than 0.05) and decreased heart rate (HR) from 81 +/- 6 to 56 +/- 5 beats/min (P less than 0.001). Plasma renin activity (PRA) decreased from 4.4 +/- 1.1 to 2.4 +/- 0.8 ng . ml-1 . 3 h-1 (P less than 0.05). A specific antagonist of the vasoconstrictor activity of vasopressin, d(CH2)5MeTyrAVP (10 micrograms/kg), completely blocked the cardiovascular and renin responses to vasopressin. A selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng . kg-1 . min-1), increased MAP from 112 +/- 4 to 128 +/- 6 mmHg (P less than 0.001) and decreased HR from 69 +/- 3 to 47 +/- 4 beats/min (P less than 0.001). PRA decreased from 5.5 +/- 1.1 to 2.7 +/- 0.2 ng . ml-1 X 3 h-1 (P less than 0.001). In contrast, a selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng . kg-1 . min-1) did not alter PRA, MAP, or HR. These results demonstrate that the acute inhibition of renin secretion by vasopressin in normally hydrated conscious dogs is due to vasoconstrictor rather than antidiuretic activity.

Duodenal acidification releases cholecystokinin.

We studied the effect of hydrochloric acid (HCl) in the proximal small intestine on release of cholecystokinin (CCK) and secretin and on exocrine pancreatic secretion in conscious dogs with gastric cannulas and modified Herrera pancreatic cannulas. Intraduodenal administration of HCl in a concentration of 50 or 100 mM at rates of 0.05, 0.1, 0.2, and 0.4 mmol/min significantly increased plasma concentration of CCK in a dose-dependent manner, whereas plasma gastrin levels decreased. The increased plasma CCK level paralleled a significant increase in pancreatic trypsin output. Plasma secretin concentration and pancreatic bicarbonate output also increased in response to the acid, and the increase was dependent on the acid loads delivered in the duodenum. Thus, in dogs, HCl in the duodenum releases both CCK and secretin to stimulate pancreatic secretion of bicarbonate as well as enzymes.

Corticotropin-releasing factor. Mechanisms to inhibit gastric acid secretion in conscious dogs.

Immunoreactivity similar to that of corticotropin-releasing factor (CRF) is found in regions of the central nervous system that modulate autonomic responses, including gastrointestinal functions. We examined the central nervous system effects of ovine CRF on gastric acid secretion in conscious dogs. Male beagle dogs (11-13 kg) were fitted with chronic intracerebroventricular cannulae and gastric fistulae. Gastric acid secretion in response to intravenously administered gastric secretory stimuli was measured by in vitro titration of gastric juice to pH 7.0 and in response to an intragastric meal by in vivo intragastric titration at pH 5.0. Plasma gastrin was determined by radioimmunoassay. CRF microinjected into the third cerebral ventricle decreased pentagastrin-stimulated gastric acid secretion for 3 h (P less than 0.01) dose-dependently (0.2-6.0 nmol X kg-1). CRF did not inhibit histamine-stimulated gastric secretion but significantly (P less than 0.01) decreased the secretory response after 2-deoxy-D-glucose for 3 h. The gastric inhibitory action of intracerebroventricularly administered CRF on pentagastrin-stimulated gastric acid secretion was completely abolished by ganglionic blockade with chlorisondamine. The opioid antagonist, naloxone, and the vasopressin antagonist, [1-deaminopenicillamine,2-(O-methyl) tyrosine,8-arginine]-vasopressin, significantly suppressed the inhibitory effect of CRF on gastric acid secretion stimulated by pentagastrin. In contrast, truncal vagotomy did not prevent the inhibition of gastric acid secretion induced by CRF. CRF (0.2-2.0 nmol X kg-1) administered intracerebroventricularly decreased gastric acid secretion stimulated by 200-ml liquid meals containing 8% peptone. CRF did not affect plasma gastrin concentrations. These results indicate that CRF microinjected into the third cerebral ventricle inhibits gastric acid secretion in conscious dogs. CRF-induced inhibition of gastric acid secretion appears to be mediated by the sympathetic nervous system and, in part, by opiate and vasopressin-dependent mechanisms.

The Influence of Sodium Intake on Physiological Responses to Angiotensin II in Conscious Dogs.

The renin-angiotensin system (RAS) is suppressed either by high sodium intake or by high levels of angiotensin II (A II). Therefore in prior studies it has been difficult to sort out the influence on the cardiovascular homeostases of different levels of A II and different levels of sodium in the diet respectively. The present study examines the quantitative effects of A II on mean arterial blood pressure (MABP), electrolyte excretion and hormone secretion in conscious dogs on low, normal and high sodium intake with the endogenous RAS blocked with continous intravenous infusion of enalapril (MK-421). Fourteen dogs on three different Na diets, low, normal and high (5, 30 and 250 mmol/day), were infused continously with enalapril, 4 mg/kg/day and studied with superinfused A II at rates of 0, 1, 3, 6 and 12 ng/kg/min., each period lasting one week. Convening enzyme inhibitor (CEI) decreased MABP equally in dogs on low and normal sodium intake to about 80% of control, but did not have a significant effect in dogs on high sodium intake. The initial infusion of angiotensin II at the lowest rate had a pronounced effect on MABP in the normal and high sodium states, but had no effect on MABP in the sodium depleted dogs. However, at the higher rates of infusion, the angiotensin II increased the pressure to a similar degree at all levels of sodium intake. All four dogs in the high sodium group developed circulatory difficulties at the 6 or 12 ng level of A II infusion: One hemorrhaged in the feces, one developed congestive failure, and in the other two the arterial pressure remained elevated an average of 23 mm Hg after removal of all drugs. Plasma renin activity increased in all groups after CEI; however, renin secretion was suppressed by much smaller rates of angiotensin II infusion in the normal and sodium loaded dogs than in the sodium depleted dogs. CEI suppressed plasma aldosterone 30% in the low sodium dogs but by a lesser percentage in the normal sodium dogs; plasma aldosterone increased in all groups after A II. The present study indicates that when the endogenous RAS is blocked with CEI, small increments in angiotensin II infusion rate can cause almost linear increments in the chronic level of mean arterial pressure at varying levels of sodium intake. Also A II infusion and high dietary sodium can have independent effects on both plasma renin activity and plasma aldosterone concentration.