Interaction between arginine vasopressin and angiotensin II receptors in the central regulation of sodium balance

We speculated that the influence of lateral preoptic area (LPO) in sodium balance, involves arginine(8)-vasopressin (AVP) and angiotensin (ANG II) on Na+ uptake in LPO. Therefore, the present study investigated the effects of central administration of specific AVP and ANG 11 antagonists (d(CH2)(5)-Tyr (Me)-AVP (AAVP) and [Adamanteanacetyl(1), 0-ET-D-Tyr(2), Val(4), Aminobutyryl(6), Arg(8.9)]-AVP (ATAVP) antagonists of V-1 and V-2 receptors of AVP. Also the effects of losartan and CGP42112A (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively), was investigated on Na+ uptake and renal fluid and electrolyte excretion. After an acclimatization period of 7 days, the animals were maintained under tribromoethanol (200 mg/kg body weight, intraperitonial) anesthesia and placed in a Kopf stereotaxic instrument. Stainless guide cannula was implanted into the LPO. AAVP and ATAVP injected into the LPO prior to AVP produced a reduction in the NaCl intake. Both the AT(1) and AT(2) ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO. AVP injection into the LPO increased sodium renal excretion, but this was reduced by prior AAVP administration. The ATAVP produced a decreased in the natriuretic effect of AVP. The losartan injected into LPO previous to AVP decreased the sodium excretion and the CGP 421122A also decreased the natriuretic effect of AVP. The AVP produced an antidiuresis effect that was inhibited by prior administration into LPO of the ATAVP. The AAVP produced no change in the antidiuretic effect of AVP. These results suggest that LPO are implicated in sodium balance that is mediated by V-1, V-2, AT(2) and AT(2) receptors. (c) 2005 Elsevier B.V All rights reserved.

Dissociation between the circulating renin-angiotensin system and angiotensin II receptors in central losartan-induced hypertension

Losartan, an AT1 angiotensin II (ANG II) receptor non-peptide antagonist, induces an increase in mean arterial pressure (MAP) when injected intracerebroventricularly (icv) into rats. The present study investigated possible effector mechanisms of the increase in MAP induced by icv losartan in unanesthetized rats. Male Holtzman rats (280-300 g, N = 6/group) with a cannula implanted into the anterior ventral third ventricle received an icv injection of losartan (90 µg/2 µl) that induced a typical peak pressor response within 5 min. In one group of animals, this response to icv losartan was completely reduced from 18 ± 1 to 4 ± 2 mmHg by intravenous (iv) injection of losartan (2.5-10 mg/kg), and in another group, it was partially reduced from 18 ± 3 to 11 ± 2 mmHg by iv prazosin (0.1-1.0 mg/kg), an alpha1-adrenergic antagonist (P<0.05). Captopril (10 mg/kg), a converting enzyme inhibitor, injected iv in a third group inhibited the pressor response to icv losartan from 24 ± 3 to 7 ± 2 mmHg (P<0.05). Propranolol (10 mg/kg), a ß-adrenoceptor antagonist, injected iv in a fourth group did not alter the pressor response to icv losartan. Plasma renin activity and serum angiotensin-converting enzyme activity were not altered by icv losartan in other animals. The results suggest that the pressor effect of icv losartan depends on angiotensinergic and alpha1-adrenoceptor activation, but not on increased circulating ANG II.

Nitric oxide and anglotensin II receptors mediate the pressor effect of angiotensin II: A study in conscious and zoletil-anesthetized rats

The circumventricular structures of the central nervous system and nitric oxide are involved in arterial blood pressure control, and general anesthesia may stimulate the central renin-angiotensin system. We therefore investigated the central role of angiotensin 11 and nitric oxide on the regulation of systemic arterial blood pressure in conscious and anesthetized rats. METHODS: Rats with stainless steel cannulae implanted into their lateral ventricle were studied. We injected the AT(1) and AT(2) angiotensin 11 receptor antagonists, losartan and PD123319, L-NAME, 7-nitroindazole (nitric oxide synthetase inhibitors), and FK409 (nitric oxide donor agent) into the lateral ventricles. Mean arterial blood pressure (MAP) was recorded in conscious and zoletil-anesthetized rats. RESULTS: Mean +/- (SEM) baseline MAP was 117.5 +/- 2 mm Hg. Angiotensin II injected into the brain lateral ventricle increased MAP from 136.5 +/- 2 min Hg to 138.5 +/- 4 mm Hg (Delta 16 +/- 3 mm Hg to Delta 21 +/- 3 mm Hg) for all experimental groups versus control from 116 +/- 2 mm Hg to 120 +/- 3 mm Hg (Delta 3 +/- 1 mm Hg to A5 +/- 2 mm Hg) (P < 0.05). L-NAME or 7-nitroindazole enhanced the angiotensin II pressor effect (P < 0.05). Prior injection of losartan and PD123319 decreased the angiotensin 11 pressor effect and the enhancement effect of L-NAME and 7-nitroindazole (P < 0.05). Zoletil anesthesia did not interfere with the effects of angiotensin 11, AT,, AT2 antagonists, or nitric oxide synthetase inhibitors. CONCLUSIONS: Endogenous nitric oxide functions tonically as a central inhibitory modulator of the angiotensinergic system. AT, and AT2 receptors influence the angiotensin 11 central control of arterial blood pressure. Zoletil anesthesia did not interfere with these effects. (Anesth Analg 2007;105:1293-7)

Brain versus peripheral angiotensin II receptors in hypovolaemia: Behavioural and cardiovascular implications

1. Angiotensin (Ang)II is involved in responses to hypovolaemia, such as sodium appetite and increase in blood pressure, Target areas subserving these responses for AngII include the cardiovascular system in the periphery and the circumventricular organs in the brain.2. Conflicting data have been reported for the role of systemic versus brain AngII in the mediation of sodium appetite.3. The role for systemic AngII and systemic AngII receptors in the control of blood pressure in hypovolaemia is well established. In contrast with systemic injections, i.c.v injections of AngII non-peptide AT(1) and AT(2) receptor antagonists, such as losartan and PD123319, do not reduce arterial pressure in sodium-depleted (furosemide injection plus removal of ambient sodium for 24 h) rats. Thus, brain AngII receptors are likely not important for cardiovascular responses to hypovolaemia induced by sodium depletion.4. Intracerebroventricular injections of losartan or PD 123319 increase arterial pressure when injected at relatively high doses. This hypertensive effect is unlikely to be an agonist effect on brain AngII receptors, Increases in arterial pressure produced by i.c.v, losartan are attenuated by lesions of the tissue surrounding the anterior third ventricle (AV3V). The hypertensive effect of i.c.v, AngII is abolished by lesions of the AV3V.5. Hypertension induced by AngII receptor antagonists is consistent with hypotension induced by AngII acting in the brain, However, the full physiological significance of this hypotensive effect mediated by brain AngII receptors remains to be determined.

Role of angiotensin II and vasopressin receptors within the supraoptic nucleus in water and sodium intake induced by the injection of angiotensin II into the medial septal area

In this study we investigated the effects of the injection into the supraoptic nucleus (SON) of non-peptide AT1- and AT2-angiotensin II (ANG II) receptor antagonists, DuP753 and PD123319, as well as of the arginine-vasopressin (AVP) receptor antagonist d(CH2)5-Tyr(Me)-AVP, on water and 3% NaCl intake induced by the injection of ANG II into the medial septal area (MSA). The effects on water or 3% NaCl intake were assessed in 30-h water-deprived or in 20-h water-deprived furosemide-treated adult male rats, respectively. The drugs were injected in 0.5 µl over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. Antagonists were injected at doses of 20, 80 and 180 nmol. Water and sodium intake was measured over a 2-h period. Previous administration of the AT1 receptor antagonist DuP753 into the SON decreased water (65%, N = 10, P<0.01) and sodium intake (81%, N = 8, P<0.01) induced by the injection of ANG II (10 nmol) into the MSA. Neither of these responses was significantly changed by injection of the AT2-receptor antagonist PD123319 into the SON. on the other hand, while there was a decrease in water intake (45%, N = 9, P<0.01), ANG II-induced sodium intake was significantly increased (70%, N = 8, P<0.01) following injection of the V1-type vasopressin antagonist d(CH2)5-Tyr(Me)-AVP into the SON. These results suggest that both AT1 and V1 receptors within the SON may be involved in water and sodium intake induced by the activation of ANG II receptors within the MSA. Furthermore, they do not support the involvement of MSA AT2 receptors in the mediation of these responses.

Interaction between supraoptic nucleus and septal area in the control of water, sodium intake and arterial blood pressure induced by injection of angiotensin II

We investigated the effects of injection into the supraoptic nucleus (SON) of losartanand PD 123319 (nonpeptide AT(1) and AT(2)- angiotensin II [ANG II] receptor antagonists, respectively); d(CH2)(5)-Tyr(Me)-AVP (AVPA; an arginine-vasopressin [AVP] V-1 receptor antagonist), FK 409 (a nitric oxide [NO] donor), and N-W-mtro-(L)-arginine methyl ester ((L)-NAME; an NO synthase inhibitor) oil water intake, sodium chloride 3% (NaCl) intake and arterial blood pressure induced by injection of ANG 11 into the lateral septal area (LSA). Mate Holtzman rats (250-300 g) were implanted with cannulae into SON and LSA unilaterally. The drugs were injected in 0.5 mul over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. ANG II was injected at a dose of 10 pmol. ANG II antagonists and AVPA were injected at doses of 80 nmol. FK 409 and (L)-NAME were injected at doses of 20 and 40 mug, respectively. Water and NaCl intake was measured over a 2-h period. Prior administration of losartan into the SON decreased water and NaCl intake induced by injection of ANG II. While there was a decrease in water intake, ANG II-induced NaCl intake was significantly increased following injection of AVPA. FK 409 injection decreased water intake and sodium intake induced by ANG II. L-NAME alone increased water and sodium intake and induced a pressor effect. (L)-NAME-potentiated water and sodium intake induced by ANG II. PD 123319 produced no changes in water or sodium intake induced by ANG II. The prior administration of losartan or AVPA decreased mean arterial pressure (MAP) induced by ANG II. PD 123319 decreased the pressor effect of ANG II to a lesser degree than losartan. FK 409 decreased the pressor effect of ANG II while (L)-NAME potentiated it. These results suggest that both ANG II AT, and AVP V, receptors and NO within the SON may be involved in water intake, NaCl intake and the pressor response were induced by activation of ANG II receptors within the LSA. These results do not support the involvement of LSA AT(2) receptors in the mediation of water and NaCl intake responses induced by ANG II, but influence the pressor response. (C) 2004 Elsevier B.V. All rights reserved.

Effects of angiotensin and vasopressin V-1 receptors on water and sodium intake induced by injection of vasopressin into lateral septal area

The specific arginine(8)-vasopressin (AVP) V, receptors antagonist (AAVP) was injected (20, 40 and 80 nmol) into the lateral septal area (LSA) to determine the effects of selective septal V, receptor on water and 3% sodium intake in rats. Was also observed the effects of losartan and CGP42112A (select ligands of the AT(1) and AT(2) ANG II receptors, respectively) injected into LSA prior AVP on the same appetites. Twenty-four hours before the experiments, the rats were deprived of water. The volume of drug solution injected was 0.5 mul. Water and sodium intake were measured at 0.25, 0.5, 1.0 and 2,0 h. Injection of AVP reduced the water and sodium ingestion vs. control (0.15 M saline). Pre-treatment with AAVP (40, 80 and 160 nmol) did not alter the decrease in the water ingestion induced by AVP, whereas AAVP abolished the action of AVP-induced sodium intake. Losartan (40, 80 and 160 nmol) did not alter the effect of AVP on water and sodium intake, whereas CGP42112A (20, 40 and 60 nmol) at the first 30 min increased water ingestion. Losartan and CGP42112A together increased the actions of AVP, showing more pronounced effects than when the two antagonists were injected alone. The results showed that AVP inhibited the appetites and these effects were increased by the AAVP. The involvement of angiotensinergic receptors in the effects of AVP is also suggested. (C) 2004 Elsevier B.V. All rights reserved.

Vasopressin and angiotensin receptors of the medial septal area in the control of mean arterial pressure induced by vasopressin

Introduction. Brain arginine(8)-vasopressin (AVP), through the V-1a- and V-2-receptors, is essential for the maintenance of mean arterial pressure (MAP). Central AVP interacts with the components of the renin-angiotensin system, which participate in MAP regulation. This study all to determine the effects of V-1a-, V-2- and V-1a/V-2-AVP selective antagonists and AT(1)- and AT(2)-angiotensin II (Ang II) selective antagonists on the MAP induced by AVP injected into the medial septal area (MSA) of the brain.Materials and methods. Male Holtzman rats with stainless steel cannulae implanted into the MSA were used in experiments. Direct MAP was recorded in Conscious rats.Results. AVP administration into the MSA caused a prompt and potent pressor response in a dose-dependent fashion. Pretreatment with the V-1a- and V-2-antagonists reduced, whereas prior injection of the V-1a/V-2-antagonist induced a decrease in the MAP that remained below the baseline. Both AT(1)- and AT(2)-antagonists elicited a decrease, While simultaneous injections of two antagonists were more effective in decreasing the MAP induced AVP.Conclusion. These results indicate there is a synergism bell the V-1a- and V-2-AVP, and AT(1)- AT, and AT(2)-Ang II receptors in the MSA in the regulation of MAP.

Involvement of the AT1 receptor in the venoconstriction induced by angiotensin II in both the inferior vena cava and femoral vein

Although angiotensin II-induced venoconstriction has been demonstrated in the rat vena cava and femoral vein, the angiotensin II receptor subtypes (AT1 or AT2) that mediate this phenomenon have not been precisely characterized. Therefore, the present study aimed to characterize the pharmacological receptors involved in the angiotensin II-induced constriction of rat venae cavae and femoral veins, as well as the opposing effects exerted by locally produced prostanoids and NO upon induction of these vasomotorresponses. The obtained results suggest that both AT1 and AT2 angiotensin II receptors are expressed in both veins. Angiotensin II concentration–response curves were shifted toward the right by losartan but not by PD 123319 in both the vena cava and femoral vein. Moreover, it was observed that both 10−5 Mindomethacin and 10−4 M L-NAME improve the angiotensin II responses in the vena cava and femoral vein. In conclusion, in the rat vena cava and femoral vein, angiotensin II stimulates AT1 but not AT2 to induce venoconstriction, which is blunted by vasodilator prostanoids and NO.

Comparative study of analytical methods by direct and first-derivative UV spectrophotometry for evaluation of losartan potassium in capsules

O losartano potássico é um agente anti-hipertensivo não peptídico, que exerce sua ação por bloqueio específico dos receptores da angiotensina II. Este trabalho propôs a validação e aplicação de métodos analíticos orientados ao controle de qualidade de losartano potássico 50 mg na forma farmacêutica cápsula, utilizando a espectrofotometria direta e derivada de primeira ordem na região do UV. Baseado nas características espectrofotométricas de losartano potássico, um sinal a 205 nm do espectro de ordem zero e um sinal a 234 nm do espectro de primeira derivada foram adequados para a quantificação. Os resultados foram usados para comparar essas duas técnicas instrumentais. O coeficiente de correlação entre as respostas e as concentrações de losartano potássico na faixa de 3,0-7,0 mg L-1 e 6,0-14,0 mg L-1 para espectrofotometria direta e derivada de primeira ordem em solução aquosa, respectivamente, foi de (r) of 0,9999 para ambos os casos. Os métodos foram aplicados para quantificação de losartano potássico em cápsulas obtidas de farmácias de manipulação locais e demonstraram ser eficientes, fáceis de aplicar e de baixo custo. Além disso, não necessitam de reagentes poluentes e requerem equipamentos economicamente viáveis.

Characterization of a Local Renin-Angiotensin System in Rat Gingival Tissue

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of subtypes of adrenergic and angiotensinergic antagonists on the water and sodium intake induced by adrenaline injected into the paraventricular nucleus

The present experiments were conducted to investigate die role of the alpha(1A)-, alpha(1B)-, beta(1)-, beta(2)-adrenoceptors, and the effects of losartan and CGP42112A (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively) on the water and sodium intake elicited by paraventricular nucleus (PVN) injection of adrenaline. Male Holtzman rats with a stainless steel cannula implanted into the PVN were used. The ingestion of water and sodium was determined in separate groups submitted to water deprivation or sodium depletion with the diuretic furosemide (20 mg/rat). 5-Methylurapidil (an alpha(1A)-adrenergic antagonist) and ICI-118,551 (a beta(2)-adrenergic antagonist) injected into the PVN produced a dose-dependent increase, whereas cyclazosin (an alpha(1B)-adrenergic antagonist) and atenolol (a beta(1)-adrenergic antagonist) do not affect the inhibitory effect of water intake induced by adrenaline. on the other hand, the PVN administration of adrenaline increased the sodium intake in a dose-dependent manner. Previous injection of the alpha(1A) and beta(1) antagonists decreased, whereas injection of the alpha(1B) and beta(2) antagonists increased the salt intake induced by adrenaline. In rats with several doses of adrenaline into PVN, the previous administration of losartan increased in a dose-dependent manner the inhibitory effect of adrenaline and decreased the salt intake induced by adrenaline, while PVN CGP42112A was without effect. These results indicate that both appetites are mediated primarily by brain AT(1) receptors. However, the doses of losartan were more effective when combined with the doses of CGP42112A than given alone p < 0.05, suggesting that the water and salt intake effects of PVN adrenaline may involve activation of multiple angiotensin II (ANG II) receptors subtypes. (C) 2003 Elsevier B.V. All rights reserved.

Interaction between paraventricular nucleus and medial septal area on the renal effects induced by adrenaline

The aim of the present study was to analyze the role of alpha(1),alpha(2)-adrenoceptors, and the effects of losartan and PD123319 (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively) injected into the paraventricular nucleus (PVN) on the diuresis, natriuresis, and kaliuresis induced by administration of adrenaline into the medial septal area (MSA). Male Holtzman rats with a stainless steel cannula implanted into the MSA and bilaterally into the PVN were used. The administration of adrenaline into the MSA increased in a dose-dependent manner the urine, sodium, and potassium excretions. The previous administration of prazosin (an alpha(1)-adrenoceptor antagonist) injected into the PVN abolished the above effects of adrenaline, whereas yohimbine (an a-adrenoceptor antagonist) doesn't affect the diuresis, natriuresis, and kaliuresis induced by adrenaline. Pretreatment with losartan into the PVN decreased in a dose-dependent manner the urine, sodium, and potassium excretions induced by MSA administration of adrenaline (50 ng), while PVN PD123319 was without effect. These results indicate that urinary and electrolyte excretion effects induced by adrenaline into the MSA are mediated primarily by PVN AT, receptors. However, the doses of losartan were more effective when combined with the doses of PD123319 than given alone, suggesting that the urinary, natriuretic, and kaliuretic effects of MSA adrenaline may involve activation of multiple angiotensin II receptors subtypes into the PVN. (C) 2004 Elsevier B.V All rights reserved.

Expression of renin-angiotensin system signalling compounds in maternal protein-restricted rats: effect on renal sodium excretion and blood pressure

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Importância da região anteroventral do terceiro ventrículo (AV3V) no controle cardiovascular e do equilíbrio hidroeletrolítico

The maintenance of the arterial pressure in normal levels is important for the homeostasis of body fluids. The central nervous system regulating sympathetic and parasympathetic autonomic efferent can adjust arterial pressure which allows animals or human to face different daily activities with the best performance. Different central areas are responsible for the control of autonomic discharges to cardiovascular system and many of them are also involved in the control of fluid electrolyte balance. One of these areas is the tissue surrounding the anteroventral third ventricle (AV3V region) localized in the forebrain and a main central site for angiotensin II receptors and osmoreceptors. The AV3V lesions impair the development of many models of experimental hypertension in rats and the pressor responses to different stimuli. Lesions of the AV3V region also reduce dipsogenic responses to angiotensin II, central cholinergic activation, water deprivation and increase in plasma osmolarity, atrial natriuretic peptide secretion produced by body fluid expansion and the increase in renal excretion to central cholinergic activation. Recent evidence also suggests the participation of AV3V region in pressor responses produced by the activation of medullary mechanisms.