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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study examined the effect of an angiotensin II AT1 or AT2 receptor antagonist on the impairment of the pressure diuresis and natriuresis response produced by nitric oxide (NO) synthesis blockade. N omega-nitro-L-arginine methyl ester (L-NAME, 37 nmol.kg-1.min-1) lowered renal blood flow and reduced the slopes of the pressure diuresis and natriuresis responses by 44 and 40%, respectively. Blockade of AT1 receptors with valsartan increased slightly sodium and water excretion at low renal perfusion pressure (RPP). Blockade of AT2 receptors with PD-123319 had no effect on renal function. The administration of valsartan or PD-123319 to rats given L-NAME had no effect on the renal vasoconstriction induced by NO synthesis blockade. In addition, in rats given L-NAME, valsartan elevated baseline excretory values at all RPP studied, but it had no effect on the sensitivity of the pressure diuresis and natriuresis response. However, the administration of PD-123319 to L-NAME-pretreated rats shifted the slopes of the pressure diuresis and natriuresis responses toward control values, indicating that the impairment produced by NO synthesis blockade on pressure diuresis is dependent on the activation of AT2 angiotensin receptors.
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PMID:Effect of interactions between nitric oxide and angiotensin II on pressure diuresis and natriuresis. 937 9

The octapeptide hormone, angiotensin II, binds to two major subtypes of cell surface receptors: the AT1 and the AT2 angiotensin receptors. The important physiological and pathophysiological effects of angiotensin II on cardiovascular regulation and salt-water balance are mediated by the AT1 receptor subtype. As a consequence of the outstanding clinical success of angiotensin-converting enzyme inhibitors, the appearance of AT1 receptor inhibitors in the therapy of hypertension and other cardiovascular diseases was preceded with great expectations. The available experimental and clinical data indicate that the first AT1 receptor inhibitor, losartan, has the same therapeutic potential as angiotensin-converting enzyme inhibitors, but it does not evoke the angiotensin-independent side-effects of ACE inhibitors, such as dry cough or angioedema. The physiological importance and the biochemical, molecular biological and pharmacological properties of AT1 and AT2 receptors are reviewed in this paper, and a summary of the available clinical data is presented.
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PMID:[AT1 angiotensin receptor inhibition as a new therapeutic possibility]. 941 27

Angiotensin II (Ang II) appears to exert its contractile and growth-promoting effects through the AT1 receptor subtype, whereas the AT2 subtype may have growth-inhibitory and proapoptotic properties. Recently, some data have challenged this emerging concept. To clarify the role of AT1 and AT2 receptors, we treated Wistar rats that were infused with Ang II (120 ng/kg/min subcutaneously by osmotic minipump), with the AT1 antagonist losartan (10 mg/kg/d in the drinking water) and the AT2 antagonist PD123319 (30 mg/kg/d subcutaneously by osmotic minipump) for 21 days. At the end of the study, tail-cuff systolic blood pressure was 106+/-2.8 mm Hg in untreated rats and 108+/-2.0 mm Hg in rats infused with Ang II that received losartan, whereas it rose to 158+/-4.9 mm Hg in Ang II-infused rats and 158+/-3.0 mm Hg in rats infused with Ang II rats and PD123319 (the two latter groups P<.01 versus the two other groups). Heart weight, and aorta cross-section/body weight ratio were higher in Ang II-infused rats than in controls and were significantly reduced in Ang II-infused rats that received losartan (P<.05). Wire-myograph-mounted coronary, renal, mesenteric, and femoral small arteries from Ang II-infused rats and Ang II-infused rats receiving PD123319 had a greater media, media cross-section, and media/lumen ratio than vessels from untreated or Ang II-infused rats treated with losartan. These results support the concept that in Wistar normotensive rats infused for 3 weeks with angiotensin II, growth in the heart, aorta, and coronary, renal, mesenteric, and femoral small arteries is mediated by the AT1 receptor; the results show little evidence of a role of AT2 receptors in mediating angiotensin II effects in this experimental paradigm.
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PMID:Effects of AT1 and AT2 angiotensin receptor antagonists in angiotensin II-infused rats. 945 50

Ureteral obstruction causes infiltration of the kidney by monocytes/macrophages. This infiltrate is significantly reduced by administration of an angiotensin-converting enzyme (ACE) inhibitor but not by a specific angiotensin II type 1 receptor (AT1 receptor) antagonist. Chemoattractants and cell surface adhesive molecules mediate monocyte/macrophage infiltration. Rats with unilateral ureteral obstruction (UUO) of 1, 3, or 5 days duration were untreated or given enalapril or SC-51316 in the drinking water. We measured the mRNA levels of monocyte chemoatactic peptide 1 (MCP-1), a chemoattractant, and levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), two cell surface adhesion proteins. MCP-1 mRNA increased significantly after 1 day of UUO and increased further through 5 days of UUO in the obstructed kidney. ICAM-1 mRNA also increased significantly after 1 day but steadily declined through 5 days of UUO in the obstructed kidney. VCAM-1 mRNA did not increase significantly until after 3 days of UUO and increased further through 5 days of obstruction. Enalapril or SC-51316 treatment had no significant effect on ICAM-1 mRNA levels. MCP-1 mRNA levels were reduced but remained significantly elevated. Enalapril significantly blunted the increase in VCAM-1 mRNA levels and VCAM-1 protein determined by immunocytochemistry; SC-51316 had no significant effect. Thus changes in VCAM-1 levels may account for the differential effect of enalapril and SC-51316 on monocyte/macrophage infiltration of the kidney during ureteral obstruction.
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PMID:Differential effects of ACE and AT1 receptor inhibition on chemoattractant and adhesion molecule synthesis. 953 Feb 75

A previous study in conscious dogs showed that the normal hypertensive response to short-term nitric oxide synthesis inhibition was markedly attenuated during angiotensin II-AT1 receptor inhibition. However, whether angiotensin plays an important cardiovascular role in the dog during long-term nitric oxide synthesis inhibition has not been determined and was therefore the goal of this investigation. Studies were conducted in 16 conscious dogs that received angiotensin AT1 receptor inhibition with L158809 (N = 8) or vehicle (N = 8) for 12 d. During the last 6 d of this infusion, nitric oxide synthesis was inhibited by infusing NG-nitro-L-arginine methyl ester intravenously at 37.1 nmol/kg/min. In both the AT1 and vehicle groups, nitroarginine infusion significantly decreased the acetylcholine depressor response, glomerular filtration rate, renal plasma flow, and heart rate, and increased arterial pressure and renal vascular resistance in a similar manner, whereas it caused little change in the urinary excretion of sodium and water or in plasma renin activity. In conclusion, the long-term responses of arterial pressure, renal hemodynamics, and the renal excretion of sodium and water to nitric oxide synthesis inhibition were not significantly influenced by blockade of angiotensin AT1 receptors with L158809 in the dog.
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PMID:Cardiovascular-renal responses to long-term nitric oxide inhibition during angiotensin II-AT1 receptor inhibition. 954 74

The vertebrate renin-angiotensin system controls cardiovascular, renal and osmoregulatory functions. Angiotensin II (ANG II) is the most potent hormone of the RAS but in some vertebrate animals angiotensin III (Val4-ANG III) may be a hormone. We studied the effects of some angiotensins and mammalian ANG II receptor antagonists on nasal salt gland function and arterial blood pressure in conscious white Pekin ducks. Nasal salt gland fluid secretion (NFS) was induced by a 10 ml.kg-1 bw i.v. injection of a NaCl solution (1000 mosmol.kg-1 H2O) and maintained by a continuous i.v. infusion of the same solution at a rate of 0.97 ml.min-1. There was a positive linear correlation between nasal fluid [Na+] and osmolality, between [Na+] and [K+], and also between the rate of NFS and [Na+] and [K+]. [Asp1, Val5]-ANG II (1 nmol.kg-1 i.v.) inhibited NFS but did not change ionic concentrations. Val4-ANG III (1 or 5 nmol.kg-1) and ANG I (1-7) (20 nmol.kg-1) had no effect on NFS. [Sar1, Ile8]-ANG II (SARILE) acted as an ANG II receptor agonist and resulted in a prolonged and complete inhibition of NFS. The AT1 receptor antagonist, losartan (DuP 753) and the AT2 receptor antagonist, PD 123319 both failed to block the inhibitory effect of [Asp1, Val5]-ANG II on the nasal salt glands. [Asp1, Val5]-ANG II (2 nmol.kg-1 i.v.) increased mean arterial blood pressure (MABP), whereas the same dose of [Asn1, Val5]-ANG II (teleost) had only 30% of the pressor potency of the avian ANG II. Neither 1 nor 5 nmol.kg-1 of Val4-ANG III i.v. nor 20 nmol.kg-1 of ANG I (1-7) had any measurable effect on MABP. SARILE blocked completely the pressor response to [Asp1, Val5]-ANG II but the AT1 antagonists losartan and CGP 48933 and the AT2 antagonist PD 123319 all failed to block the pressor response to [Asp1, Val5]-ANG II. These results have substantiated an important role of the nasal salt gland in potassium regulation and highlighted a pharmacological dimorphism of saralasin, namely agonist and antagonist to angiotensin II-mediated inhibition of nasal salt gland function and pressor response, respectively. Using specific nonpeptidergic angiotensin II receptor antagonists, we have confirmed the distinct pharmacology of the avian angiotensin II receptors in a nongallinaceous species and the absence of significant angiotensin I (1-7) and angiotensin II effects on the cardiovascular system and nasal salt gland.
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PMID:Effects of ANG II and III and angiotensin receptor blockers on nasal salt gland secretion and arterial blood pressure in conscious Pekin ducks (Anas platyrhynchos). 959 62

We studied the effect of angiotensin (ANG) peptides and their C- and N-terminal fragments, microinjected bilaterally into the hypothalamic paraventricular nucleus (PVN) of male Wistar rats, on arginine vasopressin (AVP) release into the blood and drinking. ANG II (1-8) and the C-terminal ANG III (2-8) at 0.1-100 pmol/200 nl induced a dose-dependent increase in AVP release with a maximum of 26.45+/-6.0 and 31.86+/-7.0 pg/ml, respectively, vs 1.6+/-2.0 pg/ml in vehicle treated controls (P<0.001). The highest dose of ANG II and ANG III also induced drinking responses of 4.3+/-0.78 and 2.91+/-0.54 ml water/15 min, respectively. Bilateral pretreatment of the PVN with the AT1 receptor antagonist losartan (4 nmol/200 nl) inhibited ANG II- and ANG III-induced AVP release and drinking. Different doses of the C-terminal ANG IV (3-8), ANG (4-8) or ANG (5-8) peptides did not induce AVP release or drinking. The N-terminal ANG (1-7) peptide induced a dose-dependent increase in AVP release (maximum 8.5+/-3.5 pg/ml after 100 pmol) but the effect was much less potent than that induced by the same dose of ANG II or ANG III. ANG (1-7) failed to induce a drinking response. Pretreatment of the PVN with losartan or the AT2 receptor antagonist, PD 123177 (4 nmol/200 nl), inhibited the 100 pmol ANG (1-7)-induced AVP release. The N-terminal ANG (1-4) peptide did not affect AVP release or drinking at any dose tested. Our data demonstrate that the C-terminal ANG II (1-8) and ANG III (2-8), but not shorter fragments, can induce AVP release and drinking response via AT1 receptors in the PVN. The N-terminal ANG (1-7) was less potent in stimulating AVP release than ANG II or ANG III and had no influence on drinking. Thus, the presence of both arginine2 and phenylalanine8 in the angiotensin peptide sequence appears to be important to elicit AVP release and drinking from the PVN in vivo.
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PMID:Sensitivity of hypothalamic paraventricular nucleus to C- and N-terminal angiotensin fragments: vasopressin release and drinking. 963 Mar 97

Angiotensin II mediates its effects through angiotensin receptors. The use of specific angiotensin receptor ligands and the cloning of these receptors allows their classification. So far, the AT1, AT2 and atypical angiotensin II receptors are recognised. The AT1 receptor is responsible for the classical effects of the renin-angiotensin system such as vasoconstriction, renal salt and water retention, central osmo-control and stimulation of cell growth. The function of the AT2 receptor is far from clear but this receptor appears to be important in fetal development, cell growth inhibition and differentiation processes. This review describes the angiotensin receptors and focuses on the possible functions of the AT2 receptor.
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PMID:Receptors and their classification: focus on angiotensin II and the AT2 receptor. 965 52

Angiotensin (ANG) II is a powerful and phylogenetically widespread stimulus to thirst and sodium appetite. When it is injected directly into sensitive areas of the brain, it causes an immediate increase in water intake followed by a slower increase in NaCl intake. Drinking is vigorous, highly motivated, and rapidly completed. The amounts of water taken within 15 min or so of injection can exceed what the animal would spontaneously drink in the course of its normal activities over 24 h. The increase in NaCl intake is slower in onset, more persistent, and affected by experience. Increases in circulating ANG II have similar effects on drinking, although these may be partly obscured by accompanying rises in blood pressure. The circumventricular organs, median preoptic nucleus, and tissue surrounding the anteroventral third ventricle in the lamina terminalis (AV3V region) provide the neuroanatomic focus for thirst, sodium appetite, and cardiovascular control, making extensive connections with the hypothalamus, limbic system, and brain stem. The AV3V region is well provided with angiotensinergic nerve endings and angiotensin AT1 receptors, the receptor type responsible for acute responses to ANG II, and it responds vigorously to the dipsogenic action of ANG II. The nucleus tractus solitarius and other structures in the brain stem form part of a negative-feedback system for blood volume control, responding to baroreceptor and volume receptor information from the circulation and sending ascending noradrenergic and other projections to the AV3V region. The subfornical organ, organum vasculosum of the lamina terminalis and area postrema contain ANG II-sensitive receptors that allow circulating ANG II to interact with central nervous structures involved in hypovolemic thirst and sodium appetite and blood pressure control. Angiotensin peptides generated inside the blood-brain barrier may act as conventional neurotransmitters or, in view of the many instances of anatomic separation between sites of production and receptors, they may act as paracrine agents at a distance from their point of release. An attractive speculation is that some are responsible for long-term changes in neuronal organization, especially of sodium appetite. Anatomic mismatches between sites of production and receptors are less evident in limbic and brain stem structures responsible for body fluid homeostasis and blood pressure control. Limbic structures are rich in other neuroactive peptides, some of which have powerful effects on drinking, and they and many of the classical nonpeptide neurotransmitters may interact with ANG II to augment or inhibit drinking behavior. Because ANG II immunoreactivity and binding are so widely distributed in the central nervous system, brain ANG II is unlikely to have a role as circumscribed as that of circulating ANG II. Angiotensin peptides generated from brain precursors may also be involved in functions that have little immediate effect on body fluid homeostasis and blood pressure control, such as cell differentiation, regeneration and remodeling, or learning and memory. Analysis of the mechanisms of increased drinking caused by drugs and experimental procedures that activate the renal renin-angiotensin system, and clinical conditions in which renal renin secretion is increased, have provided evidence that endogenously released renal renin can generate enough circulating ANG II to stimulate drinking. But it is also certain that other mechanisms of thirst and sodium appetite still operate when the effects of circulating ANG II are blocked or absent, although it is not known whether this is also true for angiotensin peptides formed in the brain. Whether ANG II should be regarded primarily as a hormone released in hypovolemia helping to defend the blood volume, a neurotransmitter or paracrine agent with a privileged role in the neural pathways for thirst and sodium appetite of all kinds, a neural organizer especially in sodium appetit
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PMID:Angiotensin, thirst, and sodium appetite. 967 90

We studied the acute effects of cadmium third ventricle injections on renal excretion of water, sodium and potassium in rats previously submitted to an oral water load equivalent to 10% of their body weight. Injections of cadmium chloride (0.03, 0.3, and 3.0 nmol/rat) significantly increased sodium and potassium renal excretion without changing urine flow. Pretreatment with losartan, an angiotensin II AT1 receptor antagonist (10.8 nmol/rat into the third ventricle 10 min before central cadmium administration) inhibits the natriuretic effect of this metal, being unable to reverse its kaliuretic effect. Pretreatment with gadolinium, a calcium-channel blocker (0.3 nmol/rat into the third ventricle 20 min before central cadmium administration) abolishes both the natriuretic and the kaliuretic response of cadmium. The data clearly show that cadmium injections into the third ventricle disturb central regulation of renal function leading to an increased renal loss of sodium and potassium. It is also evident that the natriuretic action of the metal depends on an increase in brain angiotensin II release. Also, the functional integrity of calcium channels is required for the expression of both the natriuretic and the kaliuretic effects of the metal.
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PMID:Natriuretic and kaliuretic effects of central acute cadmium administration in rats. 968 77


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