Disease relevance of ANGIOTENSIN II

• Our study suggests that a central neuropeptide, probably AII, is involved in the maintenance of the exaggerated salt appetite in this model of hypertension [1].
• The 1-des Asp, 8-Ile AII analogue, conversely, induced a consistent, larger, dose-related renal blood flow increase, with significantly less hypotension over a wide dose range [2].
• Inhibition of IAC by AII was prevented by intracellular application of guanosine 5'-O-2-(thio)-diphosphate but was not affected by pre-incubation of cells with pertussis toxin [3].
• AIMS: We evaluated the direct effect of angiotensin II (AII) on the pathogenesis of immune mediated colitis using angiotensinogen deficient homozygous (Atg-/-) mice [4].
• In the present study, specific receptors for angiotensin II (AII) were also analyzed in a murine fibroblast cell line (R3T3) and a rat pheochromocytoma cell line (PC-12) [5].

High impact information on ANGIOTENSIN II

• Our results suggest a central role for rANP and AII in genetic hypertension; they may act as mutual antagonists in brain areas involved in control of blood pressure and fluid regulation [6].
• Here we have studied binding sites for rat atrial natriuretic peptide(6-33) (rANP) and AII in the brains of spontaneously (genetic) hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY) rats, by quantitative autoradiography [6].
• Injection of angiotensin II (AII) into the cerebral ventricles at doses as low as 1 pmol h-1 results in a marked stimulation of salt and water ingestion in the rat [1].
• Evidence that AII is produced in the central nervous system independently of the circulating renin-angiotensin system (RAS) raises the possibility that endogenous brain AII is involved in the physiological regulation of thirst [1].
• Intracranial injection of angiotensin II (AII) or activation of the cerebral isorenin-angiotensin system with intracranial renin causes an immediate thirst and a delayed sodium appetite in the rat [7].

Chemical compound and disease context of ANGIOTENSIN II

• Losartan is the first recently approved drug against hypertension disease that competes with the biological action of angiotensin II (AII) at the AT1 receptor [8].
• SK&F 108566 (30 micrograms/kg.min) or enalapril (1 mg/kg), at doses which inhibited the pressor effects of AII or AI, respectively, but had no significant influence on base-line GFR and ERPF, significantly attenuated the glycine-induced glomerular hyperfiltration and hyperemia [9].
• In acute conditions, LL rats exhibited an unspecific hypersensitivity to AII and NE [10].
• Inhibitors of angiotensin converting enzyme block AII production, are orally active and have been used successfully in the control of hypertension and in the treatment of congestive heart failure [11].
• Infusion of the angiotensin II (AII) competitive antagonist, [Sar1, Ile8]AII, before the vasopressin infusion abolished the hyperresponsiveness to vasopressin in the renal artery stenosis rabbits and resulted in changes in mean arterial pressure and TPR that were approximately of the same magnitude as the controls [12].

Biological context of ANGIOTENSIN II

• Conversely, the number of AII binding sites was higher in both young and adult SHR compared with WKY rats [6].
• In contrast, AII had a greater pressor effect (P less than 0.001) and produced more femoral vasoconstriction (P less than 0.001) than AIII [2].
• For the kidney, the threshold doses of AII and AIII were identical (2.5+/-0.27 vs. 2.3+/-0.35 pmol/100 ml renal blood flow, with similar dose-response curves [2].
• Thus, there is direct cross-talk between insulin and AII signaling pathways at the level of both tyrosine phosphorylation and PI 3-kinase activation [13].
• Furthermore, our finding that both human transgenes are expressed in brain regions of RA+ mice known to be involved in cardiovascular regulation raises the possibility that augmented local production of AII and increased activation of AT-1 receptors at these sites is involved [14].

Anatomical context of ANGIOTENSIN II

• TIVCC resulted in marked activation of plasma AII and ET in plasma, right atrium, lung, and renal medulla which was further localized to cardiomyocytes, pulmonary, and renal epithelial cells [15].
• These results suggest that AII or AIII stimulates the Na+/K+ pump in cultured aortic muscle cells by increasing its Na+ supply [16].
• The cellular binding activity was associated with isolated PEC plasma membranes, and after density gradient fractionation of solubilized membranes, AII binding activity was primarily associated with molecules of m.w. of around 50,000 [17].
• In bovine adrenal zona fasciculata (AZF) cells, angiotensin II (AII) may stimulate depolarization-dependent Ca2+ entry and cortisol secretion through inhibition of a novel potassium channel (IAC), which appears to set the resting potential of these cells [3].
• These results show that macrophages express specific receptors for AII and related peptides that are responsible for most of the uptake of AII by macrophages [17].

Associations of ANGIOTENSIN II with other chemical compounds

• We conclude that the renal vascular receptor differs sufficiently from systemic angiotensin receptors that heptapeptide analogues of AII will be useful in exploring angiotensin's role in states characterized by disordered renal perfusion and function [2].
• Femoral and renal blood flow and their responses to angiotensin II (AII) and its heptapeptide analogue, 1-des Asp AII (AIII), were measured with an electromagnetic flowmeter in 26 dogs [2].
• Neither the PLC antagonist neomycin nor PLC-generated second messengers prevented IAC expression or mimicked the inhibition of this current by AII [3].
• CONCLUSIONS: The DD genotype was associated with an increased reactivity to PE in vivo and potentiating effect of exogenous AII in vitro [18].
• We conclude that AII in the pituitary does not significantly alter either basal PRL levels or metoclopramide- and TRH-induced PRL responses in normal subjects on low and high salt diets [19].

Gene context of ANGIOTENSIN II

• Endothelin-1 (ET-1) and angiotensin II (AII) are potent vasoconstrictor hormones which regulate tissue perfusion and blood pressure [20].
• In summary, in human resistance arteries, contractions to ET-1 are mediated by ETA- and ETB-receptors while those to AII are exclusively mediated by AT1-receptors [20].
• Association and dissociation studies performed with 125I-AII on human myometrium membranes revealed that AII had a very high affinity for AT2 receptors, with a Kd of 0.01 nM (association rate constant K1 = 1.056 x 10(12) mol-1 min-1; dissociation rate constant K2 = 0.003 min-1) [21].
• In this study, we show that the octapeptide hormone angiotensin II (AII), apparently acting through the AT1 G-protein-coupled receptor, is also a mitogen for RIE-1 cells [22].
• At a dose of 50 ng/ml, TNF alpha inhibited AVP-stimulated ACTH release by 30% and blocked the effect of AII [23].

Analytical, diagnostic and therapeutic context of ANGIOTENSIN II

• Western blotting confirmed robust PDI expression and shift to membrane fraction after incubation with angiotensin II (AII, 100 nm, 6 h) [24].
• Plasma angiotensin concentrations were measured in a longitudinal study of the vascular, renal, and adrenal responses to infusions of angiotensin II (AII) in the maturing newborn lamb [25].
• Recent studies have suggested a possible causative relationship between elevated plasma levels of Angiotensin II (AII) and the vasoconstriction associated with conventional cardiopulmonary bypass [26].
• Losartan, a selective angiotensin II (AII) type I receptor antagonist, may protect against myocardial stunning and arrhythmia in ischemia and reperfusion [27].
• Incubating the cell monolayers with thoroughly washed sperm cells obtained from the intact cauda epididymides of rats increase (P less than 0.01) the AII content of the cell culture medium, with a parallel decline (P less than 0.01) in the AI concentration [28].

References