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K A Duggan

Publications and source records attributed to K A Duggan.

At least 19 recordsLinked to original sources
PubMed2002

Dysregulation of angiotensin II synthesis is associated with salt sensitivity in the spontaneous hypertensive rat.

(1) Salt sensitive hypertension, which occurs as a result of treatment with nitric oxide synthase inhibitors, is associated with a loss of the usual down-regulatory effect of dietary sodium on angiotensin II (Ang II) synthesis. In the spontaneous hypertensive rat (SHR), which suffers a relative NO deficiency, the hypertension is in part salt sensitive. We sought to determine therefore whether the salt sensitive component to the hypertension was associated with a loss of the regulatory effect of dietary sodium on Ang II synthesis. (2) Male SHR were placed on low, intermediate or high salt diets for 4 weeks and their blood pressure recorded. After 4 weeks, blood was collected for determination of renin, angiotensinogen, Ang I, Ang II and aldosterone concentrations, as well as ACE activity. (3) The increase in systolic blood pressure in rats on the high salt diet was significantly greater than in those on the low (P < 0.005) and intermediate salt diets (P < 0.0005). Plasma renin and aldosterone concentrations and ACE activity decreased with increasing dietary sodium. However, the concentrations of Ang II and angiotensinogen both increased in the rats on the high salt diet (Ang II: P < 0.05; angiotensinogen: P < 0.05). (4) We conclude that the hypertension in the SHR is in part salt sensitive and that this salt sensitive component is associated with a loss of the normal down-regulatory effect of dietary sodium on Ang II and angiotensinogen synthesis.

Aldosterone↗
PubMed2002

Salt-sensitive hypertension resulting from nitric oxide synthase inhibition is associated with loss of regulation of angiotensin II in the rat.

In the Dahl salt-sensitive hypertensive rat, a diet containing L-arginine, the natural substrate for nitric oxide synthase, abrogates the hypertension. We postulated that nitric oxide synthase inhibition might induce a salt-sensitive form of hypertension and that this salt sensitivity might be linked to a loss of the regulatory effect of sodium ingestion on angiotensin II (Ang II) and angiotensinogen. Male Wistar-Kyoto rats were randomised to a diet containing 0.008 %, 2.2 % or 4.4 % sodium chloride and to treatment with the NO synthase inhibitor L-NAME (10 mg kg(-1) day(-1)) in the drinking water, or drinking water alone (Controls) for 4 weeks. Blood pressure was measured by tail cuff plethysmography twice weekly. After 4 weeks, the rats were anaesthetised and truncal blood collected for determination of angiotensinogen, renin, angiotensin I (Ang I), Ang II and aldosterone concentrations as well as angiotensin-converting enzyme (ACE) activity. Systolic blood pressure increased with increasing dietary sodium intake in the L-NAME-treated rats (P < 0.05). Plasma renin and aldosterone concentrations decreased with increasing dietary sodium intake in both Control and L-NAME-treated rats. Ang I and ACE activity were unchanged by increasing dietary sodium intake. In contrast, the plasma concentration of Ang II and angiotensinogen increased with increasing dietary sodium (P < 0.05 and P < 0.005, respectively). Treatment with the Ang II receptor blocker, losartan, reversed the blood pressure increase. We conclude that treatment with L-NAME induces an increase in blood pressure that is at least in part salt sensitive. Further, the salt-sensitive component appears to be Ang II-dependent, as it was associated with increasing plasma Ang II levels and could be reversed by treatment with an Ang II receptor antagonist.

Aldosterone↗
PubMed2001

Effects of nitric oxide synthase inhibition on angiotensin receptors and metabolism in the pregnant hypertensive rat.

Endothelial dysfunction and a consequent decrease in nitric oxide production have been implicated in the pathogenesis of pre-eclampsia. A prominent feature of the pre-eclamptic syndrome is a loss of the pregnancy-induced refractoriness to infused pressor agents, such as angiotensin. In this study, we sought to determine whether a decrease in nitric oxide production might be linked via changes in angiotensin II receptors and angiotensin II metabolism to changes in pressor sensitivity to infused angiotensin II. Pregnant and non-pregnant spontaneously hypertensive rats (SHRs) were randomly allocated to receive 5 mg x kg(-1) x day(-1) N(G)-nitro-L-arginine methyl ester (L-NAME) in the drinking water or drinking water alone from days 7 to 14 of gestation. Steady-state metabolic clearance studies of angiotensin II were then performed, or tissues were harvested for angiotensin II receptor studies. Treatment with L-NAME caused an increase in systolic pressure (P<0.001) in both pregnant and non-pregnant rats, while urinary protein excretion increased only in the pregnant SHRs (P<0.001). Plasma angiotensin II levels were significantly increased in the L-NAME-treated SHRs compared with controls (non-pregnant, P<0.0005; pregnant, P<0.01). The metabolic clearance rate of angiotensin II was decreased by L-NAME treatment in non-pregnant SHRs (P<0.05), but was increased by L-NAME treatment in the pregnant rats (P<0.01). In the aorta, the angiotensin II receptor number increased after treatment with L-NAME in both non-pregnant (P<0.0005) and pregnant (P<0.05) SHRs, and the dissociation constant increased in the non-pregnant SHRs (P<0.005). Thus treatment of SHRs with L-NAME increased blood pressure, as well as the circulating angiotensin II concentration and vascular angiotensin II receptor expression. However, treatment with L-NAME did not affect pressor sensitivity to infused angiotensin II. We conclude, therefore, that although a decrease in nitric oxide production is associated with changes in angiotensin II concentrations and receptor numbers, it does not induce changes in pressor sensitivity to infused angiotensin II in the SHR.

Analysis of Variance↗
PubMed2000

Factors regulating renal angiotensin-converting enzyme activity in the rat.

Changes in angiotensin-converting enzyme (ACE) activity appear to be important in mediating the natriuresis which ensues after administration of an oral or gastric sodium load. In this study, we sought to determine the time course of the changes in ACE activity in the kidney which occur after sodium ingestion. In addition, we sought to investigate mechanisms which might underlie these changes. Angiotensin-converting enzyme activity was measured by generation of histidyl-leucine in homogenates of kidneys harvested at varying time-points after gastric sodium administration. The effects of intravenous sodium loading, solution osmolality and of changes in renal nerve activity were also investigated. Intragastric instillation of both the sodium-containing solution and its iso-osmotic urea control solution resulted in significant increases in renal ACE activity (NaCl: P < 0.0005; Urea: P < 0.01). The increase in renal ACE activity after gastric sodium loading was more prolonged than after the urea control (P < 0.025, NaCl vs. urea at 90 min). This prolonged increase in renal ACE activity appeared to reflect a response to absorbed sodium as intravenous sodium administration caused a significant increase in renal ACE activity at 90 min (P < 0.0005). In contrast to these stimuli which increased renal ACE activity, renal denervation caused a significant decrease in ACE activity in the kidney (P < 0.05). We conclude that gastric sodium loading increases renal ACE activity. This effect appears to be due initially to a response to an increase in gastric lumenal osmolality and later to absorbed sodium. These changes in renal ACE activity are not mediated by a decrease in renal nerve activity.

Animals↗
PubMed2000

Modulation of the intrahepatic renin-angiotensin system after stimulation of the gastric sodium monitor in the rat.

Changes in the rate of formation of angiotensin II (ANG II) participate in mediating the natriuresis that occurs in direct response to a gastric sodium stimulus (upper-gut sodium monitor). As this natriuresis is also dependent on intrahepatic events, we investigated whether changes in hepatic and plasma angiotensinogen levels and hepatic angiotensin-converting enzyme (ACE) activity might explain the decrease in ANG II synthesis. Male Sprague-Dawley rats, equilibrated on a low-sodium diet, were anaesthetized and received a sodium load of 1.5 mmol/kg (using 3 x normal saline) either intragastrically or intravenously. Blood and livers were sampled before and at various times after sodium administration. ACE activity in serum and tissues was determined by generation of histidyl-leucine. Angiotensinogen was determined by radioimmunoassay of angiotensin I generated by incubation in the presence of exogenous renin. Plasma angiotensinogen had decreased significantly by 15 min after sodium administration (P<0.005), while hepatic angiotensinogen was also decreased significantly from 30 min after the sodium load (P<0.01). Hepatic ACE activity decreased in response to sodium (P<0.005) from 30 min. We conclude that stimulation of the gastric sodium monitor regulates angiotensinogen synthesis and secretion by the liver, as well as hepatic ACE activity.

Angiotensin I↗
PubMed2000

Vasoactive intestinal peptide down-regulates the intrahepatic renin-angiotensin system in the anaesthetized rat.

Gastric sodium loading results in an increase in the portal venous concentration of vasoactive intestinal peptide (VIP) and down-regulation of both the intrahepatic and circulating renin-angiotensin systems. In the present study we sought to determine whether an increase in the concentration of VIP in the portal circulation might act to down-regulate the intrahepatic and/or circulating renin-angiotensin systems. Male Sprague-Dawley rats were infused intraportally with haemaccel vehicle or VIP in haemaccel for 60 min. Livers were harvested and blood was sampled. Angiotensin-converting enzyme (ACE) activity and angiotensinogen, angiotensin I, angiotensin II and renin concentrations were measured. VIP infusion decreased hepatic ACE activity (P < 0.05), the hepatic angiotensinogen concentration (P < 0.001) and the hepatic angiotensin I concentration (P < 0.05). The plasma angiotensinogen concentration and serum ACE activity were also decreased by intraportal VIP infusion (P < 0.05 for each). Plasma renin, angiotensin I and angiotensin II concentrations were unchanged by VIP infusion. We conclude that an increase in the portal venous VIP concentration down-regulates the intrahepatic renin-angiotensin system. These changes are similar to those reported after gastric sodium loading, and we suggest, therefore, that the increase in portal venous VIP that occurs after gastric sodium is the means by which the gastric sodium sensor signals the liver to effect these changes in the renin-angiotensin system.

Angiotensin I↗
PubMed1998

Effects of enalapril on vasoactive intestinal peptide metabolism and tissue levels.

Angiotensin converting enzyme inhibitor therapy results in an increase in cardiac output without an increase in heart rate suggesting a positive inotropic effect. This cannot be explained by changes in angiotensin II and bradykinin concentrations. Angiotensin converting enzyme may also metabolise vasoactive intestinal peptide (VIP), a vasodilator and positive inotrope whose concentration in the heart declines in heart failure. We sought to determine whether changes in plasma VIP or its metabolism might explain the positive inotropic effect of angiotensin converting enzyme inhibitors. We also measured VIP in the heart to determine whether a local increase in VIP might explain this effect. Male Sprague-Dawley rats were randomised to control and enalapril groups (2 mg kg(-1) day(-1)). After 7 days, rats were anaesthetised and underwent metabolic clearance studies for VIP or had hearts, lungs and kidneys removed and snap frozen. VIP concentrations in plasma, infusate and tissue extracts were measured by radioimmunoassay. Plasma concentrations of VIP were unchanged by treatment with enalapril (control: 7.7 +/- 0.8 pmol l(-1); enalapril: 7.9 +/- 0.8 pmol l(-1) ), while the metabolic clearance rate of) VIP increased significantly (control: 10.4 +/- 1.4 ml min(-1) 100 g(-1); enalapril: 17.3 +/- 1.6 ml min(-1) 100 g(-1); p < 0.005). Secretion rate) also increased in enalapril treated rats (139.1 +/- 25.0 pmol min(-1) 100 g(-1) compared with controls (96.3 +/- 13.4 pmol min (-1) 100 g(-1); P< 0.01). VIP in the heart increased after enalapril (control: 208.4 +/- 39.0 pmol g (-1); enalapril: 928.9 +/- 123.6 fmol g(-1); P < 0.0005). Angiotensin converting enzyme inhibition increases the metabolism of VIP. However, the significant increase in the myocardial concentration of VIP may contribute to the beneficial haemodynamic inotrope effects of angiotensin converting enzyme inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Renoprotective differences between perindopril and enalapril in the diabetic hypertensive rat do not reflect glomerular angiotensin-converting enzyme activity.

1. The various angiotensin-converting enzyme inhibitors have structural differences which affect their affinities for the catalytic sites on converting enzyme. We postulated that such differences might result in differences in renoprotective efficacy. We investigated this in the diabetic spontaneous hypertensive rat. We also investigated whether these differences might reflect variations in glomerular or plasma angiotensin-converting enzyme activity. 2. One week after induction of diabetes, rats were started on antihypertensive therapy: enalapril, 10 mg.day-1.kg-1, or perindopril, 4 mg.day-1.kg-1, in the drinking water. After 3 months, the rats were killed, blood samples were taken and tissues were harvested. Angiotensin-converting enzyme activity in isolated glomeruli and plasma was measured by fluorimetric assay. Glomerular protein content was also determined. 3. Urinary protein excretion was significantly lower in perindopril-treated rats than in either controls (P < 0.0005) or enalapril-treated rats (P < 0.05). Glomerular protein content was also lower in perindopril-treated rats (P < 0.05 versus enalapril; P < 0.005 versus control). There was no difference in glomerular angiotensin-converting enzyme activity between the two inhibitors although both were lower than control values (enalapril P < 0.025; perindopril P < 0.025). Plasma angiotensin-converting enzyme activity was significantly lower in the perindopril group than in either control (P < 0.005) or the enalapril group (P < 0.01). 4. We conclude that in the spontaneous hypertensive rat with streptozotocin-induced diabetes, perindopril is more effective than enalapril in reducing proteinuria and glomerular protein accumulation. This difference does not result from differences in glomerular-converting enzyme activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Mechanisms underlying the decrease in circulating angiotensin II concentration after sodium loading.

1. Acute sodium loading causes a rapid decrease in the circulating concentration of angiotensin II (AngII), which is apparent from 5 min after sodium administration. This could result from an increase in AngII catabolism and/or a decrease in AngII synthesis/secretion. However, the major determinant of AngII synthesis is thought to be a change in plasma renin activity, which occurs over a longer time frame (15 min). 2. To investigate the mechanisms underlying the rapid decrease in plasma AngII engendered by sodium administration, we performed metabolic clearance studies in male New Zealand white rabbits before and after a hypertonic sodium load of 1.5 mmol/kg as 0.513 mol/L saline i.v. bolus. 3. The metabolic clearance rate of AngII increased significantly from 42.2 +/- 9.0 mL/min per kg before sodium to 110.8 +/- 33.7 mL/min per kg after sodium administration (P < 0.05). The calculated or theoretical secretion rate decreased from 1470.7 +/- 404.2 to 573.5 +/- 139.5 fmol/min per kg (P < 0.025) in response to sodium. 4. We conclude that an increase in AngII metabolism and a decrease in synthesis/secretion contribute to the reduction in circulating AngII, which occurs in the first 60-90 min after sodium loading.

Angiotensin II↗
PubMed1997

Stimulation of the gastric sodium monitor reduces hepatic angiotensin-converting enzyme activity.

1. The natriuresis engendered by stimulation of the gastric sodium monitor is mediated in part by a decrease in the circulating concentration of angiotensin II (AngII). This decrease is due to decrease in synthesis rather than to an increase in metabolism. We investigated the role of changes in plasma and hepatic angiotensin-converting enzyme (ACE) activity in this decrease in AngII synthesis. 2. Male Sprague-Dawley rats were equilibrated on a low-sodium diet for 7 days. On the day of experiment, rats were anaesthetized and received either a sodium load of 1.5 mmol/kg as 3 mol/L saline or an equivalent volume of an iso-osmotic urea solution by direct gastric puncture. Blood was sampled and livers were harvested at 0 and 30 min after sodium or urea administration. Angiotensin-converting enzyme was measured in serum and tissue homogenates by generation of histidyl-leucine. 3. In the liver, ACE activity decreased from control after both sodium (P < 0.005) and urea (P < 0.025) administration. The decrease was greater in the group that received saline compared with rats that received urea (P < 0.05). Serum ACE decreased in response to urea (P < 0.025) but not sodium administration. 4. We conclude that stimulation of the gastric sodium monitor results in a decrease in ACE activity in the liver. This decrease in ACE activity may be contributory to the decrease in AngII synthesis.

Angiotensin II↗
PubMed1997

Acute but not chronic angiotensin-converting enzyme inhibition induces enzyme synthesis in the glomerulus of the spontaneously hypertensive rat.

1. Treatment with angiotensin-converting enzyme (ACE) inhibitors slows the rate of progression of nephropathy in the spontaneously hypertensive rat (SHR) with streptozotocin-induced diabetes. Paradoxically, however, chronic ACE inhibitor therapy has been reported to be associated with induction of ACE in the plasma. We sought to determine whether induction also occurred in the glomerulus. 2. Seven days after induction of diabetes rats were randomized to receive perindopril (4 mg/kg per day) in the drinking water or water alone. Blood glucoses were maintained 6-10 mmol/L by daily ultralente insulin. Rats were killed after 1 and 12 weeks of ACE inhibitor therapy and the kidneys were harvested. Angiotensin-converting enzyme activity was determined in isolated glomeruli before and after removal of perindopril and reconstitution with zinc sulphate. 3. After 1 week of ACE inhibitor therapy, glomerular ACE was significantly greater after removal of perindopril than either before its removal (P < 0.025) or in the untreated controls (P < 0.025). After 12 weeks of therapy, ACE activity was significantly lower in the perindopril-treated group than in the untreated controls (P < 0.025). There was no increase in ACE activity following removal of perindopril. 4. These studies suggest that short-term ACE inhibition is associated with induction of ACE in the glomerulus. However, there was no increase in ACE activity after removal of perindopril, suggesting that induction of synthesis of this enzyme in the glomerulus does not occur during chronic ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Stimulation of gastric osmoreceptors but not the sodium monitor increases renal angiotensin-converting enzyme activity.

1. Stimulation of the gastric sodium monitor has been reported to cause a decrease in renal nerve activity and also a decrease in plasma renin activity in renal venous blood. This suggests that changes in sympathetic nerve activity and in the intrarenal renin-angiotensin system may mediate the natriuresis that occurs following gastric sodium administration. In the present study we sought to determine whether gastric sodium administration also modulates angiotensin-converting enzyme (ACE) activity in the kidney. 2. Male Sprague-Dawley rats were equilibrated on a low-sodium (0.008%) diet for 7 days. On the day of the experiment, rats were anaesthetized and kidneys were harvested and immediately snap frozen at 0 and 60 min after intragastric administration of a saline load (1.5 mmol/kg as 3 mol/L saline) or an equivalent volume of iso-osmotic urea (5.95%). Angiotensin-converting enzyme activity was determined by incubation of kidney homogenates with hippuryl-histidyl-leucine and fluorometric assay of the histidyl-leucine generated. 3. Angiotensin-converting enzyme activity in the kidney increased in response to the intragastric administration of both sodium chloride and urea. Angiotensin-converting enzyme activity increased significantly from control levels (189.9 +/- 24.3 nmol/min per g protein) by 60 min in both NaCl-and urea-treated groups (492.3 +/- 27.3 and 468.6 +/- 28.7 nmol/min per g protein, respectively; P < 0.0005). 4. We conclude that instillation of sodium chloride or isoosmotic urea into the stomach increase ACE activity in the kidney. The results of the present study suggest that this effect is due to changes in osmolality rather than stimulation of the gastric sodium monitor.

Animals↗
PubMed1997

Evidence for direct interaction of ketamine with alpha 1- and beta 2-adrenoceptors.

1. Ketamine has a number of effects that suggest that it may interact with alpha- and beta-adrenoceptors. To date, the experimental evidence for this has been indirect and has been based on physiological studies using competitive blocking agents. In the present study we sought to determine from receptor binding studies whether ketamine binds directly to alpha- and beta-adrenoceptors. 2. Membrane preparations of alpha 1- and beta 2-adrenergic binding sites were obtained from urinary bladder and urethrae of sheep. These binding sites were characterized by saturation analyses using [3H]-prazosin for alpha 1-adrenoceptor binding sites and [125I]-cyanopindolol (CYP) for the beta 2-adrenoceptor binding sites. The receptors were further characterized by displacement studies using selective and non-selective antagonists. 3. Studies in which ketamine was used to displace [3H]-prazosin revealed a Kd of 3.40 +/- 1.23 x 10(-3) mol/L for ketamine binding to alpha 1-adrenoceptors. Displacement studies of [125I]-CYP by ketamine showed a Kd of 0.35 +/- 0.03 x 10(-3) mol/L for ketamine binding to beta 2-adrenoceptors. 4. We conclude that ketamine interacts directly with both alpha 1- and beta 2-adrenoceptors and that such interactions probably explain the reported effects of this agent on the vasculature and the bronchial tree.

Adrenergic alpha-Antagonists↗
PubMed1996

Angiotensin-converting enzyme inhibition with enalapril increases the cardiac concentration of vasoactive intestinal peptide.

In patients with congestive cardiac failure, treatment with ACE inhibitors results in peripheral vasodilatation and an increase in cardiac output without an increase in heart rate, which suggests a positive inotropic effect. This cannot be explained by the changes in angiotensin II and bradykinin concentrations that occur. It has been suggested that ACE also metabolizes VIP, which is a positive inotrope. As VIP is synthetized by the heart and acts locally to increase cardiac output, we postulated that ACE inhibition would increase the myocardial concentration of VIP. Male Sprague-Dawley rats received enalapril (2 mg/kg/day) in the drinking water or no therapy for seven days. On day seven they were anaesthetized and blood sampled. The hearts and kidneys were then harvested and snap frozen by immersion in liquid nitrogen. Concentrations of VIP in plasma and tissue extracts were measured by radioimmunoassay. Plasma and renal concentrations of VIP did not change in the enalapril-treated rats. However, the myocardial concentration of VIP increased significantly in the rats receiving enalapril compared with control animals (p < 0.0005). We conclude that treatment with ACE inhibitors results in increased myocardial VIP concentrations and suggest that this may contribute to the improvement in cardiac function that occurs with these agents.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

A study of angiotensin II receptors after chronic inhibition of nitric oxide synthase in the spontaneously hypertensive rat.

1. Nitric oxide (NO) synthase inhibition, induces a sustained increase in blood pressure and amplifies the pressor response to infused angiotensin II (AngII). This study was designed to investigate the contribution of AngII receptors in the elevated blood pressure and enhanced pressor response to AngII in the spontaneously hypertensive rat (SHR) chronically treated with N(G)-nitro-L-arginine-methyl ester (L-NAME). 2. Two groups of 13 week old female SHR were housed four to a box. Group I rats received L-NAME for 7 days (2.5 mg/kg per day) in their drinking water. Group II rats received water only. Blood pressure was monitored daily by tail-cuff plethysmography. Plasma AngII was measured by radioimmunoassay. Aortic and uterine receptor binding was determined by saturation analysis using [125I]-Sar8, Ile1)AngII. Data was analysed using the computer program LIGAND. 3. Mean systolic blood pressure was significantly elevated in rats treated with L-NAME compared with the control group. Plasma AngII concentration was slightly decreased in rats treated L-NAME compared with control. Densities of both aortic and uterine AngII receptors increased significantly following NO synthase inhibition. Receptor affinity in the aorta decreased in the L-NAME group compared with control. However, uterine AngII receptor affinity was unchanged. 4. We conclude that the increased blood pressure and enhanced pressor responsiveness that occurs with chronic inhibition of NO synthesis may result partly from increased vascular AngII receptor expression.

Angiotensin II↗
PubMed1996

Angiotensin II: a humoral mediator for the gastric sodium monitor.

Natriuresis in direct response to a gastric sodium stimulus (upper-gut sodium monitor) has paradoxically only been demonstrated in humans and animals on a low-sodium diet preceding each study. It is possible that the low-sodium diet itself induces or suppresses systems that mediate or oppose the ensuing natriuresis. In this study, we sought to determine whether a system activated by this diet, the renin-angiotensin system, mediates the natriuretic response. Specifically, we sought to show whether changes in the circulating concentration of angiotensin II (ANG II) may mediate the renal response to stimulation of the gastric sodium monitor. Male New Zealand White rabbits were randomly assigned to low- (0.008%) or normal (2.2%) sodium diets. After 1 wk on the experimental diet, they received a sodium load intragastrically or intravenously, and plasma ANG II was measured at 0, 5, 10, 30, 60, and 120 min. Urine was collected for 4 h after the sodium load, and plasma sodium was measured at 0, 2, and 4 h. Urinary sodium excretion was greater in the 4 h after gastric than after intravenous sodium administration (P < 0.025) in the rabbits on the low-sodium diet. No significant difference was noted in the rabbits on the normal sodium. In rabbits on the low-sodium diet, there was an immediate and significant decline in plasma ANG II after sodium was administered both intragastrically (P < 0.025) and intravenously (P < 0.05). This decrease was greater after intragastric than intravenous sodium (P < 0.0025), and the difference was still evident at 120 min (P < 0.05). No significant difference in plasma ANG II was found in the normal diet group. We conclude, therefore, that a prolonged decrease in ANG II concentration may play a role in mediating the natriuretic response to the gastric sodium monitor.

Angiotensin II↗