Functional evidence that the central renin-angiotensin system plays a role in the pressor response induced by central injection of cabachol

We investigated the effects of losartan, an AT1-receptor blocker, and ramipril, a converting enzyme inhibitor, on the pressor response induced by angiotensin II (ANG II) and carbachol (a cholinergic receptor agonist). Male Holtzman rats (250-300 g) with a stainless steel cannula implanted into the lateral ventricle (LV) were used. The injection of losartan (50 nmol/l mul) into the LV blocked the pressor response induced by ANG II (12 ng/1 mul) and carbachol (2 nmol/ 1 mul). After injection of ANG II and carbachol into the LV, mean arterial pressure (MAP) increased to 31 + 1 and 28 + 2 mmHg, respectively. Previous injection of losartan abolished the increase in MAP induced by ANG II and carbachol into the LV (2 + 1 and 5 + 2 mmHg, respectively). The injection of ramipril (12 ng/ 1 mul) prior to carbachol blocked the pressor effect of carbachol to 7 + 3 mmHg. These results suggests an interaction between central cholinergic pathways and the angiotensinergic system in the regulation of arterial blood pressure.

Inhibitory effect of DUP-753 on the drinking responses of rats to central administration of noradrenaline and angiotensin II and to dehydration

We investigated the effect of losartan (DUP-753) on the dipsogenic responses produced by intracerebroventricular (icv) injection of noradrenaline (40 nmol/mul) and angiotensin II (ANG II (2 ng/mul) in male Holtzman rats weighing 250-300g. The effect of DUP-753 was also studied in animals submitted to water deprivation for 30 h. After control injections of isotonic saline (0.15 M NaCl, 1 mul) into the lateral ventricle (LV) the water intake was 0.2 ñ 0.01 ml/h. DUP-753 (50 nmol/mul) when injected alone into the LV of satiated animals had no significant effect on drinking (0.4 ñ 0.02 ml/h) (N = 8). DUP-753 (50 nmol/mul) injected into the LV prior to noradrenaline reduced the water intake from 2.4 ñ 0.8 to 0.8 ñ 0.2 ml/h (N = 8). The water intake induced by injection of ANG II and water deprivation was also reduced from 9.2+ 1.4 and 12.7 ñ 1.4 ml/h to 0.8 ñ 0.2 and 1.7 ñ 0.3 ml/h (N = 6 and N=8), respectively. These data indicate a correlation between noradrenergic pathways and angiotensinergic receptors and lead us to conclude that noradrenaline-induced water intake may be due to the release of ANG II by the brain. The finding that water intake was reduced by DUP-753 in water-deprived animals suggests that dehydration releases ANG II and, that AT1 receptors of the brain play an important role in the regulation of water intake induced by deprivation.

The role of angiotensin AT1 receptors in the diuretic, natriuretic, kaliuretic and blood pressure responses induced by angiotensin II activation of the median preoptic nucleus in conscious rats

We determined the effects of two classical angiotensin II (ANG II) antagonists, [Sar1, Ala8]-ANG II and [Sar1, Thr8]-ANG II, and losartan (a nonpeptide and selective antagonist for the AT1 angiotensin receptors) on diuresis, natriuresis, kaliuresis and arterial blood pressure induced by ANG II administration into the median preoptic nucleus (MnPO) of male Holtzman rats weighing 250-300 g. Urine was colected in rats submitted to a water load (5 percent body weight) by gastric gavage, followed by a second water load (5 percent body weight) 1 h later. The volume of the drug solutions injected was 0.5 µl over 10-15 s. Pre-treatment with [Sar1, Ala8]-ANG II (12 rats) and [Sar1, Thr8]-ANG II (9 rats), at the dose of 60 ng reduced (13.7 +/- 1.0 vs 11.0 +/- 1.0 +/- 1.2, respectively), whereas losartam (14 rats) at the dose of 160 ng totally blocked (13.7 +/- 1.0 vs.7.6 +/- 1.5) the urine excretion induced by injection of 12 ng of ANG II (14 rats)...

Progesterone administration to ovariectomized rats reduces water and salt intake induced by central administration of angiotensin II

We tested the effects of estradiol, progesterone and testosterone on water and salt intake induced by angiotensin II (ANG II) injected into the third ventricle of female Holtzman rats weighing 250-300 g. The water and salt ingestion observed after 120 min in the control experiments (injection of 0.5µl of 0.15 M NaCl into the third ventricle) was 1.6 ñ 0.3 ml (N = 10) and 0,3 ñ 0.1 ml (N = 8) in intact rats, respectively, and 1.4 ñ 0.3 ml (N = 10) and 0.2 ñ 0.1 (N = 8) in ovariectomized rats, respectively. ANG II injected in intact rats (4, 6, 12, 25, and 50 ng, icv, in 0,5 µl saline) induced an increase in water intake (4.3 ñ 0.6, 5.4 ñ 0.7, 7.8 ñ 0.8, 10.4 ñ 1.2, 11.2 ñ 1.4 ml/120 min, respectively) ( N = 43). The same doses of icv ANG II in intact increased the 3 per cent NaCl intake (0.9 ñ 0,2, 1.4 ñ 0,3, 2,3 ñ 0.4, 2,2 ñ 0,3, and 2.5 ñ 0.4 ml/120 min, respectively) (N = 42). When administered to ovariectomized rats ANG II induced comparable amounts of water intake (4.0 ñ 0.5, 4.8 ñ 0.6 ñ 0.7, 9.6 ñ 0.8, and 10.9 ñ 1.2 ml/120 min, respectively (

Injection of ramipril into the lateral ventricle interferes with the drinking response induced by pharmacological and natural thirst stimuli

We investigated the effects of ramipril, an angiotensin I-converting enzyme (ACE) inhibitor, on water intake by male Holtzman rats (250-300 g) with cannulae implanted into the lateral ventricle. Intracerebroventricular (icv) injection of ramipril (1 µg/µl) significantly reduced drinking in response to subcutaneous (sc) injection of isoprenaline (100 µg/kg) from 8.49 + or - 0.69 to 2.96 + or - 0.36 ml/2 h, polyenthyleneglycol (PEG) (30 percent w/v, 10 ml/kg) from 9.51 + or - 2.20 to 1.6 + - 0.34 ml/2 h or water deprivation for 24 h from 12.61 + or - 0.83 to 5.10 + or - 1.37 ml/2 h. Ramipril had no effect on water intake induced by cellular dehydration produced by sc injection of hypertonic saline (2 M NaCl). These results are consistent with the hypothesis that ramipril acts as an ACE-blocking agent in the brain. The possibility that ramipril is transformed to ramiprilat, the active drug, by the brain is suggested

Central angiotensin converting enzyme-blockade and thirst

1. The effect of lisinopril, a potent inhibitor of angiotensin converting enzyme (ACE), injected into the medial preoptic area (MPOA) on water intake was investigated in male Holtzman rats (200-250 g). 2. Injection of lisinopril (2 micrograms/microliters) into the MPOA abolished the water intake induced by subcutaneous (sc) injection of isoprenaline (100 per cent ) and water deprivation (90 per cent ) and drastically reduced the water intake induced by sc injection of polyethyleneglycol (60 per cent ). A small reduction of water intake induced by lisinopril was also observed 90 and 120 min after sc hypertonic saline (N = 10 for each group). 3. These results suggest that central ACE activation, particularly in the MPOA, plays an important role in the dipsogenic responses induced by the agents studied

Inhibition of renal electrolyte excretion by gabaergic pathways of the lateral hypothalamic area

Injection of gamma butyric acid (GABA) into the lateral hypothalamic area of unrestrained conscious rats caused a decrease in renal electrolyte excretion with an increase in urinary flow. When picrotoxin, a specific inhibito of gabaergic pathways, was administered, a significant increase in renal water and electrolyte excretion occured. The effect of simultaneous injection of pidrotoxin and GABA into the same site indicate that picrotoxin was less potent in reversing tyhe effect induceb by GABA than GABA was in reversing the effect of picrotoxin. We conclude that GABA acts directly on the neuronal mechanisms involved in the control of water and elecltrolyte excretion, perhaps by exerting a tonic inhibitory action on renal electrolyte excretion

Participation of opiate pathways in the lateral hypothalamic area in the control of renal electrolyte and water excretion

Injection of Met-enkephalin (0.05, 0.25 and 0.50 µg in 1 µl) solutions into the lateral hypothalamic area (LHA), of unrestrained and unanesthetized rats caused a significant decrease of sodium (0.30 ñ 0.13 to 0.07 ñ 0.01, P < 0.05) and potassium (0.61 ñ 0.17 to 0.21 ñ 0.04, P < 0.05) excretion. When the blocking agent nalaxone (0.20 µg in 1 µl) was injected alone, a signifricant increase of sodium (0.34 ñ 0.04 to 0.96 ñ 0.28, P < 0.05) and potassium (0.76 ñ 0.13 to 1.72 ñ 0.30, P < 0.05) excretion was observed. However, a dose-response relationship was not observed. However, when in another experiment naloxone was injected before Met-enkepalin into the same area, reversal of the effect of naloxone occured, with decreased sodium and potassium excretion. We conclude that the enkephalinergic pathway of the LHA when stimulated with Met-enkephalin plays an inhibitory role in the contorl of sodium and potassium excretion

Characteristics of toad bladder urinary acidification

The urinary acidification system present in the bladder of the toad Bufo marinus ictericus was investigated by means of an improved technique of mounting the membrane that minimizes the edge damage when the bladder is placed as a sheet between lucite half chambers. In ouabain-treated bladders in the absence of exogenous CO2, acification rates were similar to those observed for turtle bladder. The presence of 1%CO2 at the serosal gas phase increased proton secretion (JH). Stimulation of JH was also observed when the cell pH was decreased by back diffusion of salicylic acid added to the mucosal(M) compartment. The estimate of the passive proton permeability of this epithelium as a whole yielded values around 1 x 10**-4cm/s. The maximum pH gradient that could be established across the membrane in the short circuit condition (about 3 pH units) was taken as the apparent proton-motive force (PMF') of the system and these values were similar to those observed in the turtle bladder. Luminal membrane depolarization caused by substitution of NaCl by KCl in Ringer solution led to an increase in JH at MpH = 7.3 without altering the PMF', which suggests that the electrical potential difference across the luminal membrane in ouabain-treated bladders is negligible when M pH is sufficiently acid to abolish H+ secretion