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

Stimulation of central angiotensin receptors promotes, among others, drinking behaviour, stimulation of natriuresis and increased release of vasopressin. Angiotensin (ANG II)-containing pathways in the lamina terminalis and the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, brain areas involved in the regulation of body fluid homeostasis, have been described. All these areas express predominantly AT1 receptors. The drinking response and the vasopressin release to centrally administered ANG II are mediated by AT1 receptors, while AT2 receptors exert inhibitory effects. Evidence for the involvement of the catecholaminergic and angiotensinergic pathways in the PVN and SON in mediating the ANG II-induced release of vasopressin is presented. ANG II is released in the PVN upon local osmotic stimulation and water deprivation. Finally, we present evidence that activation of central angiotensinergic receptors, water deprivation, or hypertonicity induce transcription of immediate-early genes and expression of the respective proteins in the lamina terminalis and in the PVN and SON. The summarized data implicate ANG II as a neuromodulator/neurotransmitter in central control of body fluid and electrolyte homeostasis.
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PMID:Angiotensin as neuromodulator/neurotransmitter in central control of body fluid and electrolyte homeostasis. 773 75

Angiotensin II (Ang II) is an important regulator of proximal tubule salt and water reabsorption. Recent studies indicate that rabbit proximal tubule angiotensin II receptors are the type-1 (AT1R) subtype. We studied the effect of Ang II on proximal tubule receptor expression. Rabbits were treated with either angiotensin converting enzyme inhibitors or a low salt diet to modulate endogenous Ang II levels. In captopril-treated rabbits, liver and glomerular AT1R mRNA levels increased 242 +/- 125 and 141 +/- 60%, respectively (n = 6-7; P < 0.05), as determined by quantitative PCR. In contrast, proximal tubule AT1R mRNA levels decreased 40 +/- 11% (n = 6; P < 0.05). Binding of 125I Ang II to renal cortical basolateral membranes of captopril-treated rabbits decreased from 2.9 +/- 0.55 to 1.4 +/- 0.17 fmol/mg protein (n = 6; P < 0.025). In rabbits fed a sodium chloride-deficient diet for 4 wk, AT1R mRNA levels decreased 52 +/- 11% in liver and 43 +/- 7% in glomeruli (n = 4-5; P < 0.05), whereas they increased 141 +/- 85% (n = 5; P < 0.05) in proximal tubule. In basolateral membranes from rabbits on the sodium chloride-deficient diet, specific binding of 125I Ang II increased from 2.1 +/- 0.2 to 4.3 +/- 1.1 fmol/mg protein (n = 7; P < 0.05). To determine whether Ang II directly regulates expression of proximal tubule AT1 receptors, further studies were performed in cultured proximal tubule cells grown from microdissected S1 segments of rabbit proximal tubules and immortalized by transfection with a replication-defective SV40 vector. Incubation of these cells with Ang II (10(-11) to 10(-7) M) led to concentration-dependent increases in both AT1R mRNA levels and specific 125I Ang II binding. Pretreatment with pertussis toxin inhibited Ang II stimulation of AT1R mRNA. AT1R mRNA expression was decreased by either forskolin or a nonhydrolyzable cAMP analogue (dibutryl cAMP). Simultaneous Ang II administration overcame the inhibitory effect of forskolin but not dibutryl cAMP. These results indicate that proximal tubule AT1R expression is regulated by ambient Ang II levels, and Ang II increases AT1R mRNA at least in part by decreasing proximal tubule cAMP generation through a pertussis toxin-sensitive mechanism. Upregulation of proximal tubule AT1R by Ang II may be important in mediating enhanced proximal tubule sodium reabsorption in states of elevated systemic or intrarenal Ang II.
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PMID:Angiotensin II upregulates type-1 angiotensin II receptors in renal proximal tubule. 773 68

Stimulation of angiotensin II AT2 receptors has been shown to inhibit AT1 receptor-mediated actions in peripheral tissues. The role of AT2 receptors in the central actions of angiotensin is not well understood. In the present study, plasma vasopressin levels and water intake in response to intracerebroventricular angiotensin II (10 pmol) were determined after intracerebroventricular pretreatment with PD 123177 (1-(4-amino-3-methylphenyl)methyl-5-diphenylacetyl-4,5,6,7-tetrahy dro-1H- imidazo[4,5-c]pyridine-6-carboxylic acid-2HCl), a selective AT2 receptor antagonist (10, 100 and 1000 pmol), or with losartan (2-n-butyl-4-chloro-5-hydroxy-methyl-1-2'-(1H-tetrazole-5-yl)biphenyl-4- yl)methylimidazole, potassium salt), a specific AT1 receptor antagonist (0.2, 2 and 10 nmol). Blood samples for vasopressin determination were drawn 90 s after angiotensin II injection and the drinking response was determined in a time interval of 10 min after intracerebroventricular angiotensin II. Losartan at a dose of 2 nmol or higher completely prevented vasopressin release and drinking response to angiotensin II. The drinking response was already attenuated after pretreatment with the lowest dose of losartan. In contrast, PD 123177 potentiated the angiotensin II-induced vasopressin release (39.7 +/- 2.7 pg/ml after 1000 pmol PD 123177 vs. 21.3 +/- 2.9 pg/ml in vehicle-pretreated controls, P < 0.05). The dipsogenic response to angiotensin II was also potentiated by PD 123177 (9.5 +/- 0.7 ml after 1000 pmol PD 123177 vs. 5.1 +/- 1.3 ml in vehicle-pretreated controls, P < 0.05). Our results suggest that the angiotensin II-induced vasopressin release and drinking, mediated by central AT1 receptors, are under inhibitory control by central AT2 receptors.
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PMID:Angiotensin AT1 receptor-mediated vasopressin release and drinking are potentiated by an AT2 receptor antagonist. 776 95

The brain renin-angiotensin system has been implicated in the central regulation of the cardiovascular system, body water balance, and cyclic regulation of reproductive hormones and behaviors. It also exerts some influence over the secretion of pituitary hormones. This system appears to be complete with the necessary precursors and enzymes for the formation and degradation of biologically active forms of angiotensins and several binding subtypes that are presumed to mediate these and other functions. Much information is now available on the AT1 site which preferentially binds angiotensin II (AngII), but also binds angiotensin III (AngIII), and appears to be responsible for mediating the above described classic angiotensin physiologies and behaviors. Less is known about the functional importance of the AT2 site which also binds AngII but preferentially binds AngIII. This site has been implicated in vascular growth and cerebral blood flow. Recently, an AT4 site has been discovered and characterized that preferentially binds AngII (3-8), a fragment of AngII referred to as angiotensin IV (AngIV). This AT4 site is prominent in cerebral cortex, hippocampus, basal ganglia, cerebellum, and spinal cord, as well as several peripheral tissues including kidney, bladder, heart, spleen, prostate, adrenals, and colon. The AT4 site may mediate memory acquisition and recall and the regulation of blood flow. The function(s) of the AT4 receptor subtype in peripheral tissues is currently unknown, although it does appear to be involved in kidney blood flow.
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PMID:The angiotensin IV system: functional implications. 776 21

We have shown that unesterified, unsaturated long-chain fatty acids inhibit angiotensin II (AII) binding to receptors in adrenal glomerulosa cells. In this report, we show that oleic and arachidonic acids are specific inhibitors of the AT1 subtype of angiotensin receptor, and exert no effect on receptors of the AT2 subtype. By contrast, decanoic acid is a weak inhibitor of the AT2 subtype only. Our previous work on a post-receptor locus of inhibition by fatty acids of aldosterone biosynthesis showed that the 18-oxidase step is uniquely sensitive. In brief, the first and last steps involved in angiotensin-stimulated aldosterone secretion are particularly sensitive to inhibition by fatty acids. These results suggest a specific role for unesterified fatty acids in regulation of salt and water metabolism.
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PMID:Specificity and mechanism of fatty acid inhibition of aldosterone secretion. 778 50

An AT1-specific angiotensin II receptor antagonist (GR117289; 1 mg/kg I.V. bolus) was administered daily to ten chronically catheterized, normotensive ewes during late pregnancy (from 126 +/- 1 days) until parturition (139 +/- 1 days); five control animals received an equivalent volume of vehicle solution. Following drug administration, mean maternal blood pressure decreased from 87 +/- 1 mmHg to a minimum of 79 +/- 1 mmHg at 0.5 h (P < 0.05; n = 10) and remained low for 4-6 h without any concomitant change in fetal blood pressure or maternal and fetal heart rates. In animals fitted with flow probes, uterine blood flow decreased from 443 +/- 21 to 363 +/- 27 ml/min at 0.5 h post-drug (P < 0.05; n = 6); this change was positively correlated with the reduction in maternal blood pressure. The mean decrements in uterine and umbilical blood flows measured by steady-state infusion of tritiated water were -611 +/- 171 ml/min at 4-6 h (P < 0.05; n = 5) and -71 +/- 19 ml/min at 0.5-1 h (P < 0.05; n = 5), respectively. Significant reductions (P < 0.05; n = 10) in fetal arterial oxygen tension (-1.6 +/- 0.4 mmHg), saturation (-6.6 +/- 1.6%) and content (-0.3 +/- 0.1 mumol/ml) were evident at 0.5 h post-drug and were maintained for 6-12 h. Umbilical oxygen delivery decreased at 0.5-1 h following drug administration (P < 0.01; n = 5), but was unaccompanied by any significant change in fetal oxygen consumption. Chronic decreases in daily fetal pH and blood oxygen content occurred in GR117289-treated ewes. There were no significant differences in gestational length or neonatal outcome between vehicle- and GR117289-treated groups of ewes with single fetuses.
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PMID:Haemodynamic responses to an angiotensin II receptor antagonist (GR 117289) in maternal and fetal sheep. 778 19

The transgenic (TG) rat (mREN2)27 is characterized by overexpression of the additional mouse Ren-2d gene in the adrenal cortex with marked suppression of renal renin. We have previously shown that in salt-depleted TG rats enhanced activation of mineralocorticoid biosynthesis is associated with selective stimulation of adrenal renin. To investigate whether the local renin-angiotensin system regulates aldosterone biosynthesis in the adrenal cortex of TG rats, we studied the effects of the AT1-angiotensin subtype receptor antagonist DuP 753 on aldosterone production in 5-week-old TG rats during salt restriction. All the rats (n = 56) were shifted from regular chow to a diet containing only 0.04% NaCl for 1 week. The AT1-receptor antagonist DuP 753 (10 mg/kg per day in drinking water) was administered to 27 of these rats during low-salt diet. Subgroups of rats were killed at 0,4, and 7 days. Low-salt diet increased both adrenal renin activity (from 31 +/- 3 to 77 +/- 4 and 85 +/- 2 ng angiotensin I.h-1.mg protein-1 at 4 and 7 days, respectively; P < .001) and mRNA (by 68.4 +/- 10% and 80 +/- 17% from baseline, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of aldosterone biosynthesis by adrenal renin is mediated through AT1 receptors in renin transgenic rats. 778 84

The effect of central administration of angiotensin II (AII) on cerebrospinal fluid (CSF) formation was studied in pentobarbital-anesthetized, artificially-ventilated rats. CSF production was measured by the ventriculocisternal perfusion method with Blue Dextran 2000 as the indicator. Baseline value of CSF production was 3.35 +/- 0.08 microliters/min. Intracerebroventricular (i.c.v.) infusion of AII at rates of 0.5 and 5 pg/min significantly lowered (P < 0.01) CSF formation by 23% and 16%, respectively. In comparison, high peptide doses (50 and 500 pg/min) did not alter this parameter. The inhibitory effect of low AII doses on CSF formation was blocked by the i.c.v. AT1 receptor subtype antagonists, losartan and SK&F 108566 (2.4 and 2.7 ng/min, respectively), but not by the AT2 receptor subtype-specific agent, PD 123319 (3.8 ng/min). Peptide AII antagonists, [Sar1,Ile8]AII (5 ng/min), which binds to both AT1 and AT2 receptors, had a similar effect to those of AT1-specific blockers. It is concluded that AII, by controlling CSF formation, may influence the water and electrolyte balance in the brain.
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PMID:AT1 receptor subtype mediates the inhibitory effect of central angiotensin II on cerebrospinal fluid formation in the rat. 783 1

In this study we describe a new angiotensin antagonist [Asp1-Arg2-Val3-Tyr4-Ile5-His6-D-Ala7, (A-779)] selective for the heptapeptide angiotensin-(1-7) [Ang-(1-7)]. A-779 blocked the antidiuretic effect of Ang-(1-7) in water-loaded rats and the changes in blood pressure produced by Ang-(1-7) microinjection into the dorsal-medial and ventrolateral medulla. In contrast, A-779 did not change the dipsogenic, pressor, or myotropic effects of angiotensin II (Ang II). Also, A-779 did not affect the antidiuretic effect of vasopressin or the contractile effects of angiotensin III, bradykinin, or substance P on the rat ileum. In the rostral ventrolateral medulla, the pressor effect produced by Ang-(1-7) microinjection was completely blocked by A-779 but not by AT1 or AT2 receptor antagonists (DUP 753 and CGP 42112A, respectively). Conversely, the pressor effect produced by Ang II was not changed by A-779 but was completely blocked by DUP 753. Binding studies substantiated these observations: A-779 did not compete significantly for 125I-Ang II binding to adrenocortical membranes at up to a 1 microM concentration. Low affinity binding was also observed in adrenomedullary membranes with an IC50 greater than 10 microM. Our results show that A-779 is a potent and selective antagonist for Ang-(1-7). More importantly, our data indicate that specific angiotensin receptors mediate the central and peripheral actions of Ang-(1-7).
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PMID:Characterization of a new angiotensin antagonist selective for angiotensin-(1-7): evidence that the actions of angiotensin-(1-7) are mediated by specific angiotensin receptors. 785 Apr 77

The measurement of cavitation events in tissue in vivo would greatly assist us to better understand how pulsed high energy ultrasound (PHEUS) interacts with living tissues, especially with regard to cancer therapy. To accomplish this, we designed and built a fibre-optic hydrophone. The principle was to couple the light of a laser diode into a lightfibre and to register the ultrasound induced modification of the refractive index in tissue. In this manner, the cavitation event could be quantitatively investigated both in water and in vivo. The structure of the bubble dynamic is in reasonable agreement with theoretical predictions, and in vitro measurements. With the fibre-optic set-up, the pressure signal can also be detected. PHEUS was generated by an electromagnetic source adapted from a commercial lithotripter (Lithostar Siemens). As biological tissue we used the experimental R3327-AT1 Dunning prostate tumor growing subcutaneously in the thigh of male Copenhagen rats. The lifetime of the cavitation bubble in water increased with the energy level of the ultrasonic pulse from 250 microseconds at 13 kV capacitor voltage to 750 microseconds at 21 kV, while the lifetime inside the tumor tissue in vivo increased only from 100 microseconds at 13 kV to 220 microseconds at 21 kV capacitor voltage.
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PMID:In vivo detection of ultrasonically induced cavitation by a fibre-optic technique. 786 70


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