Ontogenetic role of angiontensin-converting enzyme in rats: Thirst and sodium appetite evaluation

We investigated the influence of captopril (an angiotensin converting enzyme inhibitor) treatment during pregnancy and lactation period on hydromineral balance of the male adult offspring, particularly, concerning thirst and sodium appetite. We did not observe significant alterations in basal hydromineral (water intake, 0.3 M NaCl intake, volume and sodium urinary concentration) or cardiovascular parameters in adult male rats perinatally treated with captopril compared to controls. However, male offspring rats that perinatally exposed to captopril showed a significant attenuation in water intake induced by osmotic stimulation, extracellular dehydration and beta-adrenergic stimulation. Moreover, captopril treatment during perinatal period decreased the salt appetite induced by sodium depletion. This treatment also attenuated thirst and sodium appetite aroused during inhibition of peripheral angiotensin II generation raised by low concentration of captopril in the adult offspring. Interestingly, perinatal exposure to captopril did not alter water or salt intake induced by i.c.v. administration of angiotensin I or angiotensin II. These results showed that chronic inhibition of angiotensin converting enzyme during pregnancy and lactation modifies the regulation of induced thirst and sodium appetite in adulthood.     

Comparison of the effects of the dipeptidyl peptidase inhibitors captopril, ramipril, and enalapril on water intake and sodium appetite of Sprague-Dawley rats

Two experiments were performed with Sprague-Dawley rats to study the effects of different inhibitors of angiotensin I converting enzyme (ACE) on water intake and sodium appetite. Subcutaneous administration of low doses of either enalapril (MK421) or ramipril (Hoe498), like captopril, was dipsogenic. Acute administration of ramipril also enhanced the drinking response to peripherally administered angiotensin I (Ang I). Higher doses inhibited the drinking response to Ang I, administered acutely either peripherally or centrally. These data provide behavioral evidence that the nonsulfhydryl inhibitors enalapril and ramipril inhibit brain converting enzyme activity and that they are considerably more potent than captopril. All three of these compounds, administered chronically in food, induced an appetite for sodium chloride (NaCl) solution. Enalapril and ramipril were more potent than captopril. Plasma renin activity was increased by each of these inhibitors, but the magnitude of the increase was not clearly related to the amount of NaCl consumed. The water intake in response to acute administration of either Ang I or isoproterenol was not reliably increased in rats treated chronically with these inhibitors.     

Central AT1 and AT2 receptors mediate chronic intracerebroventricular angiotensin II-induced drinking in rats fed high sodium chloride diet from weaning

Intracerebroventricular (ICV) angiotensin (AIl) administration stimulates central AII receptors to induce water consumption in rats. The aim of this study was to determine the role of brain AT1 and AT2 receptors in mediating chronic ICV AII-induced drinking in rats raised on normal or high sodium chloride diets from weaning. Rats were weaned at 21 days of age and placed on normal or high sodium chloride diet for 10-12 weeks. At adulthood, the animals were instrumented with brain lateral ventricular cannulas and femoral arterial catheters. Low dose chronic central AII infusion (20 ng min(-1)) significantly (P < 0.05) increased water intake in both groups of rats when compared with their respective controls of 24 h artificial cerebrospinal fluid infusions. In a separate group of high sodium fed rats, coinfusion of AII with the AT1 receptor antagonist, losartan (0.25 microg min(-1)) or the AT2 receptor blocker, PD 123319 (0.50 microg min(-1)) blocked chronic ICV AII-induced drinking. Upon reinfusion of AII water intake increased above control. Following the cessation of AII infusions, water intake returned to values not significantly different from control (P > 0.05). In contrast, in the normal sodium fed rats losartan, but not PD 123319, blocked the AII-mediated water intake. The data demonstrate that in high sodium chloride fed rats AII stimulates both central AT1 and AT2 receptors to induce drinking, while in the normal sodium chloride fed rats the peptide activates the drinking response primarily by stimulation of central AT1 receptors.     

Oestrogenic influence on brain AT1 receptor signalling on the thirst and sodium appetite in osmotically stimulated and sodium-depleted female rats

The present work was carried out to investigate the role of angiotensin II type 1 (AT(1)) receptors in nocturnal thirst and sodium appetite induced by classical models of osmotic and sodium depletion challenges in ovariectomized rats chronically treated with oil or oestradiol benzoate (EB, 20 microg per animal, s.c. daily). In both conditions, the animals were given saline or losartan (108 nmol per animal, i.c.v.), a selective AT(1) receptor blocker. Oestrogen therapy significantly reduced the water intake induced by water deprivation, sodium depletion produced by frusemide injected 24 h before, and s.c. acute frusemide plus captopril injection (FUROCAP protocol), with no alteration following s.c. hypertonic saline injection. In contrast, EB therapy decreased the salt intake induced by sodium depletion and FUROCAP protocols, with no alteration following water deprivation and s.c. hypertonic saline injection. Central AT(1) blockade inhibited the dipsogenic response induced by water deprivation, osmotic stimulation, chronic sodium depletion and FUROCAP protocols and inhibited the natriorexigenic response induced by sodium depletion in ovariectomized rats. Oestrogen therapy significantly attenuated the losartan-induced antidipsogenic and antinatriorexigenic actions following sodium depletion and FUROCAP protocols. These results indicate that ovariectomized rats express increased AT(1) receptor signalling related to thirst and sodium appetite responses. Oestrogen therapy and brain AT(1) receptor blockade weakened or markedly decreased the behavioural responses during the nocturnal period, a time at which brain angiotensinergic activity is expected to be more prominent. Finally, we demonstrated through different experimental protocols a clear-cut influence of oestrogenic status on the behavioural AT(1)-induced signalling response.     

Effect of brain serotoninergic stimulation on sodium appetite of euthyroid and hypothyroid rats

The aim of the present work was to investigate the role of the serotoninergic system in the control of sodium appetite of hypothyroid rats (HTR) by administering drugs that affect the serotoninergic activity, and to compare the same homeostatic behaviour in euthyroid rats (ETR) also given these drugs. Fenfluramine (FEN; 5.0 mg x kg(-1), I.P.), which releases serotonin in the brain, significantly reduced the intake of 1.8 % NaCl in HTR subjected to water and sodium depletion (depleted) or water, sodium and food deprivation (deprived) by 31 and 45 %, respectively, 120 min after FEN injection, compared to HTR that received vehicle alone. Similarly, administration of FEN to ETR reduced 1.8 % NaCl intake in depleted and deprived rats by 64 and 46 %, respectively. The presynaptic serotonin reuptake inhibitor fluoxetine (20.0 mg x kg(-1), I.P.) led to the inhibition of sodium appetite in HTR during the initial 30 min in depleted rats and for up to 60 min post-injection in deprived rats, while sodium appetite inhibition persisted for longer periods in ETR. The 5HT2C receptor agonist mCPP (5.0 mg x kg(-1), I.P.) caused a drastic reduction in sodium appetite in HTR and ETR in depleted and deprived rats, respectively, after 120 min. Prior administration of the 5HT2C receptor antagonist LY53857 (5.0 mg x kg(-1), I.P.) completely blocked the inhibitory action of mCPP on sodium appetite in both HTR and ETR. In summary, our results suggest that the recruitment of serotoninergic neurons involved in the modulation of sodium appetite seems to be decreased in hypothyroidism due to a probable deficiency in the cerebral signalling pathway.     

Effects of SFO lesions on salt appetite during multiple sodium depletions.

A depletion of sodium may increase sodium intake by increasing the synthesis of angiotensin (ANG) II in the blood and by stimulating ANG II receptors in the subfornical organ (SFO) of the rat. Lesions of SFO reportedly reduce these intakes. The present experiments tested the effects of SFO lesions on salt appetite after three successive depletions. After a furosemide-induced natriuresis, Long-Evans rats had free access to water- and sodium-deficient diet for 22 h. Water and 0.3 M NaCl were given for 2 h, and then the rats received regular chow, water, and 0.3 M NaCl until the next injection 5 or 7 days later. SFO lesions reduced water intake 1-2 h after each furosemide injection but not during the overnight periods. The lesions did not affect salt appetite the next day, 24-26 h after furosemide, but they did prevent the expected increase in the chronic daily 0.3 M NaCl intake after repeated depletions. The second experiment was similar to the first except that three subcutaneous injections of 100 mg/kg captopril were given at 1, 18, and 20 h after furosemide for the second depletion only. After the first depletion, the results were similar to those of the same condition of the first experiment. After the second depletion, captopril greatly reduced water intake and salt appetite in all rats including those with SFO lesions. Thus, we found that the lesion reduced chronic intake, but we did not replicate results showing large effects of SFO lesions on acute salt appetite. This residual acute appetite after SFO lesion remains dependent on the synthesis of ANG II.     

FURO/CAP: A protocol for sodium intake sensitization

We investigated if a history of FURO/CAP, a protocol that increases brain angiotensin II (ANG II), sensitizes or enhances sodium intake. A subcutaneous injection of the diuretic furosemide (FURO, 10 mg/kg) was combined with a converting enzyme inhibitor captopril (CAP, 5 mg/kg) to induce a short latency stimulated sodium (0.3 M NaCl) and water intake in a 2 h FURO/CAP test. Repeated injections of only FURO/CAP, separated by one-week interval, enhanced stimulated and spontaneous (daily) sodium intake. Stimulated fluid intake was completely suppressed when FURO/CAP was combined with two intraperitoneal injections of the ANG II type-1 receptor antagonist losartan (10, 20, or 40 mg/kg each) given within 1 h prior to the FURO/CAP test. Losartan reduced by only 35% the FURO/CAP-induced natriuresis. A history of FURO/CAP, FURO/CAP + losartan (all doses), or vehicle produced similar stimulated fluid intake when all animals received only FURO/CAP in the third final FURO/CAP test. However, a history of vehicle or FURO/CAP + losartan 10 mg/kg precluded the enhancement in spontaneous sodium intake after the third final FURO/CAP. The FURO/CAP combined with losartan (all doses) also precluded the spontaneous sodium intake enhancement in the weeks that preceded the third final FURO/CAP test. A history of only FURO/CAP, but not vehicle, also enhanced water deprivation-induced sodium appetite. The results suggest that a history of FURO/CAP enhances stimulated and spontaneous sodium intake, as well as water deprivation-induced sodium appetite, and reinforce the role of ANG II as a peptide that mediates long-term effects on behavior.     

Salt and water intake in Brattleboro rats with hypothalamic diabetes insipidus

Brattleboro rats lacking vasopressin have an elevated plasma osmolality and a stimulated renin-angiotensin system relative to Long-Evans rats (LE). The current studies were performed to elucidate the factors controlling water and salt intake in the Brattleboro rat with diabetes insipidus (DI). DI and LE rats were given the choice of water and saline solutions ranging from 0.1-1.0% to assess palatability, dialyzed with isotonic glucose to test for sodium appetite after sodium depletion, and infused intracranially with an angiotensin II analogue (saralasin) to assess the role of angiotensin II in spontaneous salt and water intake. DI rats exhibited spontaneous salt intake which was not significantly different from LE rats and increased their intake of 3.0% NaCl following sodium depletion, although less reliably than LE rats. A significant proportion of those DI rats not developing a sodium appetite showed attenuation of their diabetes following dialysis. No evidence for involvement of angiotensin II in spontaneous salt and water intake was found.     

Sodium appetite decreased by central angiotensin blockade

Disturbances in body water and electrolytes that trigger sodium appetite, such as sodium depletion or hypovolemia, are potent activators of the renin-angiotensin system. In the absence of an actual deficit in body fluids, angiotensin injections are adequate to stimulate increased sodium ingestion. To assess whether angiotensin is a significant mediator of sodium appetite induced by acute alterations in body fluids, sodium intake was examined in rats during central or peripheral angiotensin blockade. Central blockade of angiotensin receptors by intracerebroventricular (ICVT) injection of the analogue antagonist saralasin decreased (but did not eliminate) sodium intake after polethylene glycol-induced hypovolemia or sodium depletion resulting from dialysis against glucose. Conversely, peripheral blockade of angiotensin converting enzyme with orally active captopril potentiated rather than decreased sodium appetite and stimulated water intake after sodium depletion. This increased water and salt intake after peripheral inhibition of converting enzyme was reversed, however, by concurrent central blockade of angiotensin receptors. These data support the hypothesis that angiotensin participates in sodium appetite associated with acute alteration in body fluids. Furthermore, the brain is the site at which angiotensin exerts its influence on sodium appetite. While the involvement of angiotensin of brain origin is not ruled out, the change in sodium appetite after peripheral blockade of converting enzyme suggests that circulating angiotensin derived from renal renin may interact with central angiotensin receptors regulating sodium appetite.     

Characteristics of thirst and sodium appetite in mice (Mus musculus)

The intakes of water and sodium chloride (NaCl) solution were examined in mice following treatment with agents that either stimulate or mimic various components of the renin-angiotensin-aldosterone system. Injections of either angiotensin II (Ang II) or isoproterenol produced very little water intake compared with the robust responses to either intracellular dehydration or to extracellular dehydration induced by treatment with polyethylene glycol (PEG). In studies on appetite for NaCl solution, mice exhibited no spontaneous preference for 0.15 M NaCl solution over water and did not change this preference during treatment with deoxycorticosterone acetate (DOCA), a sodium-deficient diet, or after adrenalectomy. Plasma concentrations of aldosterone were increased in intact mice fed a sodium-deficient diet but were not eliminated by adrenalectomy. However, acute treatment with furosemide in combination with a sodium-deficient diet stimulated an appetite for NaCl solution. Chronic oral administration of an angiotensin I (Ang I) converting enzyme inhibitor failed to induce a NaCl appetite. These findings show that mice are refractory to the induction of either water or NaCl intake by stimuli of the renin-angiotensin-aldosterone system, stimulation that is highly effective in rats; this suggests that there may be major differences among rodents in the hormonal determinants of behaviors related to hydromineral homeostasis.     

Central AT1 and AT2 receptors mediate chronic intracerebroventricular angiotensin II‐induced drinking in rats fed high sodium chloride diet from weaning

Intracerebroventricular (ICV) angiotensin (AIl) administration stimulates central AII receptors to induce water consumption in rats. The aim of this study was to determine the role of brain AT₁ and AT₂ receptors in mediating chronic ICV AII‐induced drinking in rats raised on normal or high sodium chloride diets from weaning. Rats were weaned at 21 days of age and placed on normal or high sodium chloride diet for 10–12 weeks. At adulthood, the animals were instrumented with brain lateral ventricular cannulas and femoral arterial catheters. Low dose chronic central AII infusion (20 ng min^?1) significantly (P < 0.05) increased water intake in both groups of rats when compared with their respective controls of 24 h artificial cerebrospinal fluid infusions. In a separate group of high sodium fed rats, coinfusion of AII with the AT₁ receptor antagonist, losartan (0.25 μg min^?1) or the AT₂ receptor blocker, PD 123319 (0.50 μg min^?1) blocked chronic ICV AII‐induced drinking. Upon reinfusion of AII water intake increased above control. Following the cessation of AII infusions, water intake returned to values not significantly different from control (P > 0.05). In contrast, in the normal sodium fed rats losartan, but not PD 123319, blocked the AII‐mediated water intake. The data demonstrate that in high sodium chloride fed rats AII stimulates both central AT₁ and AT₂ receptors to induce drinking, while in the normal sodium chloride fed rats the peptide activates the drinking response primarily by stimulation of central AT₁ receptors.     

Thirst and sodium appetite after colloid treatment in rats: role of the renin-angiotensin-aldosterone system

Recent experiments indicated that rats usually develop sodium appetite 5 hr after subcutaneous injection of polyethylene glycol (PEG) solution. However, sodium appetite appeared within 30 to 60 min if the rats had been maintained on sodium-deficient diet instead of Purina chow for 2-4 days previously. Elevated levels of aldosterone paralleled the appearance of NaCl consumption in both circumstances. In the present experiments, sodium appetite was no longer potentiated by pretreatment maintenance on sodium-deficient diet when the hypersecretion of aldosterone after PEG administration was prevented by prior hypophysectomy. Conversely, sodium appetite was enhanced in PEG-treated rats when angiotensin II (AII) was produced in unusually large amounts in the brain, owing to the systemic administration of captopril. This latter effect occurred even when drinking water was withheld and plasma sodium concentrations were markedly elevated. These and other findings raise the possibility that the normal secretion of aldosterone in rats after PEG treatment might permit physiological amounts of AII to be effective in stimulating sodium appetite. Such actions would complement the accepted physiological role of the renin-angiotension-aldosterone system in the maintenance of blood pressure and sodium balance.     

Effects of exercise and anion on intake of sodium solutions in Syrian hamsters.

Previous studies have shown that hamsters have low spontaneous intakes of NaCl solutions and are refractory to induction of salt appetite. In order to examine the generality of these results, the intakes of NaCl and NaHCO3 solutions are reported for hamsters housed either in normal laboratory conditions (sedentary) or with free access to exercise wheels. Spontaneous salt intakes, as well as those induced by acute sodium depletion and treatment with either the angiotensin converting enzyme inhibitor, enalapril, or deoxycorticosterone acetate (DOCA), were measured. The intakes of NaCl and NaHCO3 were similar. Salt intakes tended to be lower in exercising than in sedentary groups. Neither acute sodium depletion nor administration of enalapril increased salt intake systematically, but treatment with DOCA increased intakes of both salt and water. These results are contrasted with the efficacy of all three treatments to induce salt appetite in rats.     

Post-ingestive signals and satiation of water and sodium intake of male rats

This study investigated the role of post-ingestive signals in the satiation of thirst or salt appetite. Post-ingestive signals, defined as those arising from the passage of fluid into the duodenum and proximal jejunum, were manipulated by implanting rats with gastric fistulas. After recovery, rats were water deprived and the following day gastric fistulas were opened (sham-drinking) or closed (control). Deprivation-induced thirst significantly increased water intake with sham-drinking rats consuming four-fold more than controls after 120 min access. Subsequently, rats were given sodium deficient chow for 48 h and the next day were administered furosemide and urine was collected. Twenty-four hours later, gastric fistulas were manipulated and rats were given water and 0.5 M NaCl and intakes were measured. After 120 min of access, rats were sacrificed and plasma sodium (pNa) and plasma-renin-activity (PRA) were measured. Furosemide resulted in a loss of 2.2 mEq of sodium in urine and sham-drinking rats consumed significantly more water and 0.5 M NaCl when compared to controls. At 120 min sham-drinking rats consumed 7.5 mEq of sodium nearly twice that of controls but had significantly lower pNa and significantly increased PRA. Interestingly, the ratio of water to 0.5 M NaCl intake was similar in both groups, with each making a mixture of ≈ 0.25 M NaCl. The results suggest that post-ingestive signals are necessary for the satiation of thirst and salt appetite.     

Water deprivation-induced sodium appetite

A water deprived animal that ingests only water efficiently corrects its intracellular dehydration, but remains hypovolemic, in negative sodium balance, and with high plasma renin activity and angiotensin II. Therefore, it is not surprising that it also ingests sodium. However, separation between thirst and sodium appetite is necessary to use water deprivation as a method to understand the mechanisms subserving sodium appetite. For this purpose, we may use the water deprivation-partial repletion protocol, or WD-PR. This protocol allows performing a sodium appetite test after the rat has quenched its thirst; thus, the sodium intake during this test cannot be confounded with a response to thirst. This is confirmed by hedonic shift and selective ingestion of sodium solutions in the sodium appetite test that follows a WD-PR. The separation between thirst and sodium appetite induced by water deprivation permits the identification of brain states associated with sodium intake in the appetite test. One of these states relates to the activation of angiotensin II AT1 receptors. Other states relate to cell activity in key areas, e.g. subfornical organ and central amygdala, as revealed by immediate early gene c-Fos immunoreactivity or focal lesions. Angiotensin II apparently sensitizes the brain of the water deprived rat to produce an enhanced sodium intake, as that expressed by spontaneously hypertensive and by young normotensive rat. The enhancement in sodium intake produced by history of water deprivation is perhaps a clue to understand the putative salt addiction in humans.The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.     

Salt appetite and lesions of the ventral part of the ventral median preoptic nucleus

Angiotensin receptors in the most ventral part of the ventral median preoptic nucleus (VVMnPO) or organum vasculosum laminae terminalis appear to be important for salt appetite to angiotensin in rats. If so, then small lesions of this region should reduce salt appetite that is dependent on angiotensin. In separate experiments, the lesion greatly reduced salt appetite after treatments with chronic oral captopril or sodium depletion. On the other hand, the VVMnPO lesion actually enhanced salt appetite to deoxycorticosterone acetate. The lesion did not affect water intake to water deprivation, combined food-water deprivation, isoproterenol, or hypertonic saline, and basal plasma osmolality and sodium values were normal. These experiments suggest that VVMnPO lesions selectively affect angiotensin-induced salt appetite without producing the gross hydrational deficits that occur with larger lesions of the ventral forebrain.     

Induction of an appetite for sodium in rats that show no spontaneous preference for sodium chloride solution--the Fischer 344 strain

Fischer 344 rats show no spontaneous preference for isotonic sodium chloride (NaCl) solution. These experiments indicate, however, that a strong appetite for this solution may be induced by various methods, including adrenalectomy, administration of a mineralocorticoid hormone, acute depletion of sodium, and treatment with inhibitors of the angiotensin I converting enzyme (ACE). These treatments were also shown to produce the expected changes in the renin-angiotensin-aldosterone system, which thus appears to be involved in the induction of an appetite for NaCl solution in this strain of rat. The intakes of NaCl induced in the Fischer 344 rats by these experimental paradigms are less than those that have been reported in either Sprague-Dawley or Wistar strains in similar paradigms. In the case of sodium depletion, the intake of NaCl solution by Fischer 344 rats appears to be more closely related to the deficit than in the other two strains. Thus, the Fischer 344 strain of rats may be a particularly good model for studies of need-related sodium appetite.     

Intracerebroventricular injection of renin in the neonatal rat reveals a precocious sodium appetite that is dissociated from renin-aroused thirst

Previous research on the ontogeny of sodium appetite in the rat has shown that sodium deficit first engenders sodium intake at 12 days of age, whereas direct stimulation of the brain renin—angiotensin system by intracranial injection of renin increases intake of NaCl solution as early as 3 days postnatally. Similar activation of brain angiotensin also increases thirst, so that the specificity of the precocious sodium intake remains undetermined. In this article we report experiments that dissociate neonatal renin-evoked sodium appetite and thirst, and establish the specificity of the appetite. Our findings confirm that sodium appetite can first be discerned at 3 days of age, and show that it rapidly develops until 12 days of age. During this developmental window, renin-evoked sodium appetite is dissociated from thirst because (a) NaCl is preferred to water, (b) the appetite develops faster than thirst, and (c) 3-day-old renin-stimulated pups will avidly lick dry NaCl. These results show that activation of brain angiotensin in the 3-day-old rat pup evokes a precocious and specific sodium appetite.© 1994 John Wiley & Sons, Inc.     

Dependence of adrenalectomy-induced sodium appetite on the action of angiotensin II in the brain of the rat

Adrenalectomized rats express a robust sodium appetite that is accompanied by high levels of blood-borne angiotensin II and is caused by angiotensin II of cerebral origin. Blood-borne angiotensin II is elevated in rats consuming NaCl after adrenalectomy, and plasma angiotensin II concentrations are increased further when the animals cannot drink a NaCl solution. These phenomena are the result of the pathological removal of aldosterone, because replacement therapy returned both sodium intake and plasma angiotensin II concentrations to preadrenalectomy levels. The adrenalectomized rat's appetite for sodium is completely suppressed by interference with the central, but not the peripheral, action of angiotensin II. These data demonstrate that the mechanism of the sodium appetite of the adrenalectomized rat is a pathological instance of the angiotensin/aldosterone synergy that governs the sodium appetite of the adrenal-intact, sodium-depleted rat. Because aldosterone has been removed, angiotensin acts alone to produce the appetite. Furthermore, the data show that it is angiotensin II of central origin that is important for sodium appetite expression.     

Importance of the renin–angiotensin system in the regulation of arterial blood pressure in conscious mice and rats

Aim: The present experiments were designed to determine the mechanism(s) for increased sensitivity to blockade of the renin–angiotensin system in mice in comparison with rats. Methods: Mice and rats, with indwelling femoral arterial and venous catheters, were chronically administered angiotensin II or pharmacological inhibitors of the renin–angiotensin system as sodium intake was altered. Results: Increasing sodium intake led to suppression of circulating renin, angiotensin II, and aldosterone in rats and mice in the absence of alterations in arterial blood pressure. Additional experiments demonstrated that continuous intravenous infusion of angiotensin II (20 ng kg^?1 min^?1) significantly increased arterial blood pressure by approximately 35 mmHg in conscious rats at all levels of sodium intake (n = 6). In contrast, arterial pressure was unaffected by angiotensin II infusion in conscious mice under conditions of low sodium intake, although arterial pressure was increased by 16 mmHg when mice were administered a high sodium intake while infused with angiotensin II (n = 6). In comparison, blockade of the endogenous renin–angiotensin system led to significantly greater effects on arterial pressure in mice than rats. Continuous infusion of captopril (30 μg kg^?1 min^?1) or losartan (100 μg kg^?1 min^?1) resulted in a 55–90% greater fall in blood pressure in conscious mice in comparison with conscious rats. Conclusion: The present studies indicate that arterial pressure in mice is more dependent upon the endogenous renin–angiotensin system than it is in rats, but mice are more resistant to the hypertensive effects of exogenous angiotensin II.