scholarly journals Seasonal dosage-dependent hypersensitivity to the angiotensin II receptor blocker, losartan. A case report and review

2013 ◽  
Author(s):  
Donald R Forsdyke
Keyword(s):  
Angiotensin Ii ◽  
Dosage Adjustment ◽  
Early Years ◽  
Receptor Subtype ◽  
Angiotensin Ii Receptor Blocker ◽  
Close Monitoring ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Geographical Regions ◽  
Long Term Treatment

Since it has been in clinical use for two decades, individual data permitting evaluation of the long-term treatment of hypertension with losartan, which blocks the dominant angiotensin-II receptor (AT 1 R), should now be available. In the present case, by dosage adjustment according to daily home blood pressure (BP) readings, a mild degree of hypertension discovered during routine examination was kept in the 130/80 (mm Hg) range over an 11 year period (2003-2013). In the early years, control was achieved with 12.5 – 25.0 mg/day and dosage adjustment was seldom needed on a seasonal basis. However, on increasing to 50 mg/day, a profound downward adjustment to 0 – 12.5 mg/day was required in hot weather. The adjustment may have prevented recurrence of drug-induced postural hypotension and renal colic. Whether the adjustment facilitated an increased nocturnal BP, as suggested by some ambulatory BP studies, was not examined. A working hypothesis, consistent with animal experiments, is that under conditions of heat-stress (e.g. vascular dilation, salt loss), there is increased expression of a countervailing, losartan-insensitive, receptor subtype (AT 2 R). By lowering BP in response to angiotensin-II, AT 2 R would facilitate fine-tuningof the AT 1 R-mediated vasoconstriction that supports BP when superficial veins dilate to enhance body cooling. This AT 2 R activity might be sufficient to explain a small summertime BP dip found in normal human subjects whose Ang II levels are not increased. The dip would be greatly enhanced when Ang II levels were increased at higher losartan dosages. Close monitoring of losartan dosage may be necessary for those living in, or travelling to, geographical regions where temperatures are seasonally or continually high, and for those engaging in activities that involve such exposure (e.g. hot yoga, Turkish baths).

scholarly journals Molecular targeting therapy with angiotensin II receptor blocker for prostatic cancer

2011 ◽  
pp. 3-13
Author(s):  
Hiroji Uemura ◽  
Hitoshi Ishiguro ◽  
Yoshinobu Kubota
Keyword(s):  
Prostate Cancer ◽  
Angiotensin Ii ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Angiotensin Ii Receptor Blocker ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Targeting Therapy ◽  
Receptor Blockers ◽  
Prostatic Diseases

Angiotensin II (Ang-II) plays a key role as a vasoconstrictor in controlling blood pressure and electrolyte/fluid homeostasis. Recently it has also been shown that this peptide is a cytokine, acting as a growth factor in cardiovascular and stromal cells. In addition, the physiological function of Ang-II seems to be similar in prostate cancer and stromal cells. It is widely assumed that Ang-II facilitates the growth of both cells, and its receptor blockers (ARBs) have the potential to inhibit the growth of various cancer cells and tumors through the Ang-II receptor type 1 (AT1 receptor). The mechanism of cell growth inhibition by ARBs has been considered to be that of suppression of the signal transduction systems activated by growth factors or cytokines in prostate cancer cells, and suppression of angiogenesis. This review highlights the possible use of ARBs as novel agents for prostatic diseases including prostate cancer and benign hypertrophy, and covers related literature.

Long-term treatment with an angiotensin II receptor blocker decreases adipocyte size and improves insulin signaling in obese Zucker rats

2009 ◽  
Vol 27 (12) ◽  
pp. 2409-2420 ◽  
Author(s):  
Marina C Muñoz ◽  
Jorge F Giani ◽  
Fernando P Dominici ◽  
Daniel Turyn ◽  
Jorge E Toblli
Keyword(s):  
Angiotensin Ii ◽  
Insulin Signaling ◽  
Term Treatment ◽  
Zucker Rats ◽  
Angiotensin Ii Receptor Blocker ◽  
Adipocyte Size ◽  
Angiotensin Ii Receptor ◽  
Long Term Treatment ◽  
Obese Zucker Rats

scholarly journals Potential role of ACE2 in coronavirus disease 2019 (COVID-19) prevention and management

2020 ◽  
Vol 8 (1) ◽  
pp. 9-19 ◽  
Author(s):  
Mengyuan Liu ◽  
Ting Wang ◽  
Yun Zhou ◽  
Yutong Zhao ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Potential Role ◽  
Human Monoclonal Antibody ◽  
Harmful Effect ◽  
Spike Protein ◽  
Angiotensin Ii Receptor Blocker ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Novel Coronavirus

AbstractCOVID-19 is the current public health threat all over the world. Unfortunately, there is no specific prevention and treatment strategy for this disease. We aim to explore the potential role of angiotensin-converting enzyme 2 (ACE2) in this regard through this literature review. As a crucial enzyme of renin-angiotensin-aldosterone system (RAAS), ACE2 not only mediates the virus entry but also affects the pathophysiological process of virus-induced acute lung injury (ALI), as well as other organs’ damage. As interaction of COVID-19 virus spike and ACE2 is essential for virus infection, COVID-19-specific vaccine based on spike protein, small molecule compound interrupting their interaction, human monoclonal antibody based on receptor-binding domain, and recombinant human ACE2 protein (rhuACE2) have aroused the interests of researchers. Meanwhile, ACE2 could catalyze angiotensin II (Ang II) to form angiotensin 1-7 (Ang 1-7), thus alleviates the harmful effect of Ang II and amplifies the protection effect of Ang1-7. ACE inhibitor and angiotensin II receptor blocker (ARB) have been shown to increase the level of expression of ACE2 and could be potential strategies in protecting lungs, heart, and kidneys. ACE2 plays a very important role in the pathogenesis and pathophysiology of COVID-19 infection. Strategies targeting ACE2 and its ligand, COVID-19 virus spike protein, may provide novel method in the prevention and management of novel coronavirus pneumonia.

Effect of the angiotensin II receptor blocker olmesartan on the development of murine acute myocarditis caused by coxsackievirus B3

2006 ◽  
Vol 110 (3) ◽  
pp. 379-386 ◽  
Author(s):  
Yoshinori Seko
Keyword(s):  
Angiotensin Ii ◽  
Fas Ligand ◽  
Acute Myocarditis ◽  
Coxsackievirus B3 ◽  
Myocardial Inflammation ◽  
Myocardial Tissue ◽  
Angiotensin Ii Receptor Blocker ◽  
Protective Effects ◽  
Ang Ii ◽  
Angiotensin Ii Receptor

Ang II (Angiotensin II) has been shown to play a pivotal role in the pathophysiology of various organs, especially the cardiovascular system. The effects of ARBs (Ang II receptor blockers) in the treatment of hypertension, congestive heart failure and myocardial fibrosis have been analysed extensively in human trials, as well as animal models, and the focus of interest is now directed to its pleiotropic effects, especially on inflammatory disorders. To investigate the effects of a new ARB, olmesartan, on immune-mediated myocardial injury, the protective effects of olmesartan on the development of murine acute myocarditis caused by CVB3 (coxsackievirus B3) were analysed. Olmesartan and a non-specific vasodilator hydralazine lowered systolic blood pressure of mice on day 7 after virus inoculation to a similar extent. Olmesartan significantly decreased myocardial inflammation compared with controls, whereas hydralazine significantly increased this. Olmesartan significantly decreased the expression of IFN-γ (interferon-γ), FasL (Fas ligand), iNOS (inducible nitric oxide synthase) and PFP (pore-forming protein) in myocardial tissue, indicating that olmesartan suppressed the activation of infiltrating killer lymphocytes. Olmesartan also decreased the expression of CVB3 genomes in myocardial tissue as well as serum levels of 8-OHdG (8-hydroxy-2′-deoxyguanosine), a biomarker of oxidative-stress-induced DNA damage. The findings suggest that olmesartan prevents myocardial damage and may improve the prognosis of patients with acute myocarditis; however, further investigations are needed before clinical use.

scholarly journals Expression of type 1 angiotensin II receptor subtypes and angiotensin II-induced calcium mobilization along the rat nephron.

1997 ◽  
Vol 8 (11) ◽  
pp. 1658-1667 ◽  
Author(s):  
N Bouby ◽  
A Hus-Citharel ◽  
J Marchetti ◽  
L Bankir ◽  
P Corvol ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Collecting Duct ◽  
At1 Receptor ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Nephron Segments

The localization of two type 1 angiotensin II receptor subtype mRNA, AT1A and AT1B, was determined by reverse transcription-PCR on microdissected glomeruli and nephron segments. The coupling sensitivity of these two receptor subtypes was evaluated by measuring variations in intracellular calcium ([Ca2+]i) elicited by angiotensin II (Ang II) in structures expressing either AT1A or AT1B mRNA, using Fura-2 fluorescence. The highest expression of AT1 mRNA was found in glomerulus, proximal tubule, and thick ascending limb. In glomerulus, AT1A and AT1B mRNA were similarly expressed, whereas in all nephron segments AT1A mRNA expression was dominant (approximately 84%). The increase in [Ca2+]i elicited by 10(-7) mol/L Ang II was highest in proximal segments (delta [Ca2+]i is approximately equivalent to 300 to 400 nmol/L) and thick ascending limb (delta [Ca2+]i is approximately equivalent to 200 nmol/L). In glomerulus and collecting duct, the response was lower (delta < 100 nmol/L). The median effective concentrations for Ang II were of the same order of magnitude in glomerulus (12.2 nmol/L), in which both AT1A and AT1B are expressed, and in cortical thick ascending limb (10.3 nmol/ L), in which AT1A is almost exclusively expressed. The Ang II-induced calcium responses were totally abolished by the AT1 receptor antagonist losartan (1 mumol/L) but not by the AT2 antagonist PD 123319 (1 mumol/L). In the absence of external Ca2+, the peak phase of the response induced by 10(-7) mol/L Ang II was reduced and shortened, suggesting that a part of the [Ca2+]i increase originated from the mobilization of the intracellular Ca2+ pool. In conclusion, these results demonstrate that in the rat kidney: (1) AT1A is the predominant AT1 receptor subtype expressed in the nephron segments, (2) glomerulus is the only structure with a relatively high AT1B mRNA content, and (3) AT1A and AT1B receptor subtypes do not differ in their efficiency for the activation of calcium second-messenger system.

Changes in angiotensin II receptor density and calcium handling during proliferation in SHR aortic myocytes

1996 ◽  
Vol 271 (6) ◽  
pp. H2330-H2338 ◽  
Author(s):  
S. F. Cortes ◽  
V. S. Lemos ◽  
C. Corriu ◽  
J. C. Stoclet
Keyword(s):  
Angiotensin Ii ◽  
Strain Difference ◽  
Calcium Handling ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Receptor Density ◽  
Angiotensin Ii Receptor ◽  
Spontaneously Hypertensive ◽  
Aortic Smooth Muscle ◽  
Wistar Kyoto

The aim of the present work was to characterize angiotensin II (ANG II) receptors and their effect on intracellular free Ca2+ concentration ([Ca2+]i) in proliferating aortic smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Independently from the proliferating state of cultures, apparent affinities of ligands (ANG II > losartan > > CGP-42112A) were consistent with the presence of AT1 receptors in primary cells from SHR and WKY. In proliferating cultures, increases in [Ca2+]i elicited by ANG II (100 nM) were dramatically attenuated or abolished in VSMCs from both strains compared with confluent and postconfluent cultures. Ca2+ releases induced by ionomycin and by ANG II in the absence of extracellular Ca2+ were also impaired in proliferating cultures. In addition, no significant strain difference was found in proliferating cultures with respect to ANG II receptor density, basal [Ca2+]i, and ANG II-induced increases in [Ca2+]i. However, ANG II receptor density significantly increased in SHR, but not in WKY VSMCs at postconfluence. Furthermore, basal [Ca2+]i was elevated in confluent and postconfluent cultures from SHR but not WKY. In confluent cultures, ANG II- and ionomycin-induced Ca2+ releases were enhanced in SHR VSMCs compared with WKY VSMCs. These results show that ANG II-induced Ca2+ release and ionomycin-sensitive Ca2+ stores are enhanced in SHR VSMCs but dramatically decreased in proliferating VSMC cultures from both strains. Mechanisms underlying these alterations remain to be defined. However, the results suggest that alterations in ANG II AT1 receptor density and in intracellular Ca2+ handling in confluent and postconfluent cultures are not associated with the proliferative phenotype of SHR VSMCs. In addition, no evidence for any change in ANG II receptor subtype associated with proliferation of VSMCs was found in either strain.

Tissue specific expression of vascular smooth muscle angiotensin II receptor subtypes during ovine pregnancy

1996 ◽  
Vol 271 (1) ◽  
pp. H212-H221 ◽  
Author(s):  
B. E. Cox ◽  
C. R. Rosenfeld ◽  
J. E. Kalinyak ◽  
R. R. Magness ◽  
P. W. Shaul
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Specific Expression ◽  
At1 Receptors ◽  
Mammary Arteries ◽  
At2 Receptors

Uteroplacentral responses to infused angiotensin II (ANG II) are less than those elicited by systemic vasculature. This does not reflect ANG II receptor (AT) downregulation but may reflect differences in AT-receptor subtypes expressed. We examined AT-receptor subtypes in smooth muscle (SM) from uterine (UA), mesenteric, renal, and mammary arteries and aorta from nulliparous (n = 12), pregnant (n = 18; 105-140 days, term = 145 days), postpartum (n = 5; 6-9 days after delivery), and nonpregnant parous (n = 14) ewes by assessing displacement of 125I-labeled ANG II binding by [Sar1, Ile8]ANG II (AT1 and AT2), losartan (AT1) PD-123319 (AT2), and CGP-42112A (AT2). AT2 receptors accounted for 75-90% of total binding in UA. Except for mammary arteries, other arteries expressed only AT1 receptors. Receptor subtype expression was not altered by reproductive state in any artery studied. With the use of autoradiography, AT2 receptors appear to predominate in media of small intramyometrial arteries, whereas AT1 receptors predominate in the luminal portion. We therefore determined which subtype mediates endothelium-derived ANG II-induced increases in UA PGI2 synthesis during pregnancy. ANG II (0.05 microM) increased PGI2 synthesis 62%, from 214 +/- 13 to 346 +/- 23 pg.mg-1.h-1 (P < 0.05). Losartan (1.0 microM) inhibited the rise in PGI2 (257 +/- 24 vs. 238 +/- 25 pg.mg-1.h-1), whereas 1.0 microM PD-123319 had no effect (231 +/- 23 vs. 337 +/- 31 pg.mg-1.h-1; P < 0.05). AT2 receptors do not mediate ANG II-induced vasoconstriction, thus differences in uteroplacental and systemic sensitivity to ANG II may reflect predominance of AT2 receptors in UASM and ANG II-induced increases in UA prostacyclin synthesis by endothelial AT1 receptors.

Charge heterogeneity of the AT1 angiotensin II receptor subtype in the rat lung

1995 ◽  
Vol 147 (1) ◽  
pp. 153-159 ◽  
Author(s):  
M Montiel ◽  
J Quesada ◽  
E Jiménez
Keyword(s):  
Angiotensin Ii ◽  
Specific Binding ◽  
Receptor Subtype ◽  
Scatchard Analysis ◽  
Ang Ii ◽  
Rat Lung ◽  
Angiotensin Ii Receptor ◽  
Charge Heterogeneity ◽  
Major Band ◽  
Receptor Sites

Abstract In order to obtain more information on the molecular structure of the angiotensin II (Ang II) binding sites from whole rat lung membranes these were characterized by isoelectric focusing (IEF) and SDS-PAGE. Whereas a single population of Ang II receptor sites was identified (Kd=2·2± 0·3 nmol/l; Bmax=203·9± 15·8 fmol/mg protein) by Scatchard analysis, using IEF three Ang II binding isoforms were observed; a major band which migrated to isoelectric point (pI) 6·7, and two minor bands with pI values of 6·5 and 6·3 Specific binding of 125I-Ang II to rat lung membrane preparations was sensitive to Losartan, a non-peptide AT1, receptor subtype antagonist, but was unaffected by the AT2 receptor subtype antagonist CGP42112A. Immunoblotting analyses on SDS gels, using a monoclonal antibody specific to the AT1, receptor, showed two immunoreactive protein species of 45 and 48 kDa. Enzymic deglycosylation using recombinant N-glycanase did not alter the molecular weight patterns of the AT1, receptor subtype. The results of the present study demonstrated that the Ang II receptor population in the whole rat lung consists solely of the AT1, receptor subtype and that the AT2 receptor subtype is absent. In addition, the data showed the existence of charge heterogeneity of the AT1, receptor subtype, and suggest that glycosylation probably does not contribute to its charge heterogeneity. Journal of Endocrinology (1995) 147, 153–159

Nephrogenesis and angiotensin II receptor subtypes gene expression in the fetal lamb

1998 ◽  
Vol 274 (6) ◽  
pp. F1062-F1069 ◽  
Author(s):  
Valérie Gimonet ◽  
Laurence Bussieres ◽  
Anissa A. Medjebeur ◽  
Bernard Gasser ◽  
Brigitte Lelongt ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mrna Expression ◽  
Mesangial Cells ◽  
Temporal Distribution ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Developmental Study ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Fetal Lamb

To investigate the role of angiotensin II (ANG II) in nephrogenesis, a developmental study of renal AT1 and AT2 receptor mRNA expression was performed in parallel with the quantitative and qualitative analysis of metanephros development in fetal lamb from 60 to 140 days of gestation. Both ANG II receptor subtypes were expressed early during nephrogenesis but displayed specific spatial and temporal distribution during gestation. High-AT2 mRNA expression took place in the outermost nephrogenic area and in the undifferentiated mesenchymal cells surrounding the ampulla; level of AT2 expression in this localization followed closely glomeruli proliferation rate and disappeared after nephrogenesis completion (>120 days). AT2 mRNA was also detected in the differentiated epithelial cells of macula densa of maturing glomeruli. Although most of AT1 mRNA labeling was found in the mesangial cells of maturing glomeruli, where it persisted after nephrogenesis completion, additional labeling was found in undifferentiated cells, in cells invading the inferior cleft of S-shaped bodies (80 days), and in medullar cells between tubules (120 days). Our results suggest that each receptor subtype has a specific role in renal morphogenesis, i.e., AT2 in mesenchymal proliferation or apoptosis and AT1 in vascular smooth muscle cells differentiation.

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