Biomedical subjects

F Amiri

Publications and source records attributed to F Amiri.

16 recordsLinked to original sources

PubMed2000

Renal angiotensin II receptors and protein kinase C in diabetic rats: effects of insulin and ACE inhibition.

It has been shown that glomerular ANG II receptors are downregulated and protein kinase C (PKC) activity is enhanced in diabetes mellitus. Therefore, we investigated glomerular and preglomerular vascular ANG II receptors and PKC isoform regulation in streptozotocin (STZ)-diabetic rats treated with insulin and/or captopril. Diabetic rats were prepared by injecting STZ (60 mg/kg). Those that developed diabetes after 48 h were treated with low or high doses of insulin, or with a low dose of insulin as well as captopril, and killed 14 days later. Their glomeruli and preglomerular vessels were purified, competitive binding studies were performed by using the ANG II antagonists losartan and PD-123319, and PKC analysis was carried out by Western blotting. Competitive binding studies showed that the AT(1) receptor was the only ANG II receptor detected on both glomeruli and preglomerular vessels of all groups. Preglomerular vascular AT(1) receptor density (B(max)) was significantly upregulated in low insulin-treated STZ rats, whereas glomerular AT(1) B(max) was downregulated. Furthermore, both the captopril- and high insulin-treated groups had less glomerulosclerosis and vascular damage than the low insulin-treated group. PKCalpha, PKCdelta, PKCepsilon, and PKCmu isoforms found in preglomerular vessels were upregulated by captopril and high insulin doses, respectively, whereas no such regulation occurred in glomeruli. We conclude that in STZ-diabetic rats ANG II receptors and PKC isoforms on preglomerular vessels and glomeruli are differentially regulated by treatment with insulin and/or captopril.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Hyperglycemia enhances angiotensin II-induced janus-activated kinase/STAT signaling in vascular smooth muscle cells.

We have shown previously that angiotensin II (Ang II) activates the janus-activated kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in vascular smooth muscle cells (VSMCs) and that activation of the JAK/STAT pathway is required for Ang II induction of VSMC proliferation. In the present study, we examined the effects of hyperglycemia (HG) on Ang II-induced JAK/STAT signaling events in cultured VSMCs. HG increases Ang II-induced JAK2 tyrosine phosphorylation and promotes a partial tyrosine phosphorylation of the enzyme under basal conditions. In addition, HG increases both basal and Ang II-induced complex formation of JAK2 with the Ang II AT(1) receptor. The extent of STAT1 and STAT3 tyrosine and serine phosphorylation are also increased under HG conditions. Furthermore, the tyrosine phosphorylation and activities of the SHP-1 and SHP-2 tyrosine phosphatases, enzymes that regulate Ang II-induced JAK2 tyrosine phosphorylation, are altered by HG. SHP-1, which is responsible for JAK2 tyrosine dephosphorylation in VSMC, is completely deactivated in HG, resulting in a prolonged duration of JAK2 phosphorylation under HG conditions. HG also enhances Ang II induction of VSMC proliferation. Taken together, these data suggest that HG augments Ang II induction of VSMC proliferation by increasing signal transduction through the JAK/STAT pathway.

Angiotensin II↗

PubMed1999

Renal angiotensin II receptor regulation and renin-angiotensin system inhibition in one-kidney, one clip hypertensive rats.

OBJECTIVE: To characterize glomerular and preglomerular vascular angiotensin II receptors during the acute phase of nonrenin-dependent one-kidney, one clip hypertension in rats, using the angiotensin II antagonists losartan and PD 123319, and to investigate their regulation after renin-angiotensin system blockade with either an angiotensin converting enzyme inhibitor, captopril, or an angiotensin II receptor antagonist, TCV-116. MATERIALS AND METHODS: One-kidney, one clip hypertension was produced in male Sprague-Dawley rats by placing a silver clip (internal diameter 0.2 mm) on the left renal artery and removing the contralateral kidney. After 1, 2 or 4 weeks, the rats were killed, and their glomerular and preglomerular vascular membranes were purified. Competitive binding studies were performed using specific angiotensin II antagonists. Similarly, one-kidney, one clip hypertension was allowed to develop for 2 weeks before treatment with captopril or TCV-116 for 2 weeks. RESULTS: Competitive binding studies showed that only the angiotensin II type 1 (AT1) receptor was detected on both glomeruli and preglomerular vessels of all groups. The vascular AT1 receptor density was significantly higher in the 1 and 2 week one-kidney, one clip groups, but the glomerular receptor density was not different in these rats compared with age-matched uninephrectomized controls. The glomerular receptor density was significantly higher in captopril-treated rats and significantly lower in TCV-116-treated rats compared with untreated and control rats, but no significant changes were detected in any groups in vascular AT1 receptor density. CONCLUSIONS: Angiotensin II receptors on preglomerular vessels and glomeruli are differentially regulated during the early phase of hypertension and after renin-angiotensin system blockade. Vascular angiotensin II receptors are upregulated in the early phase of hypertension whereas glomerular angiotensin II receptors are not However, after renin-angiotensin system blockade, glomerular but not vascular angiotensin II receptors were differentially regulated according to the type of blockade.

Angiotensin Receptor Antagonists↗

PubMed1999

Regulation of natriuretic peptide secretion by the heart.

Secreted by the heart, more specifically by atrial cardiomyocytes under normal conditions but also by ventricular myocytes during cardiac hypertrophy, natriuretic peptides are now considered important hormones in the control of blood pressure and salt and water excretion. Studies on natriuretic peptide secretagogues and their mechanisms of action have been complicated by hemodynamic changes and contractions to which the atria are constantly subjected. It now appears that atrial stretch through mechano-sensitive ion channels, adrenergic stimulation via alpha 1A-adrenergic receptors, and endothelin via its ETA receptor subtype are major triggering agents of natriuretic peptide release. With several other stimuli, such as angiotensin II and beta-adrenergic agents, modulation of natriuretic peptide release appears to be linked to local generation of prostaglandins. In all cases, intracellular calcium homeostasis, controlled by several ion channels, is considered a key element in the regulation of natriuretic peptide secretion.

Animals↗

PubMed1999

Regulation of angiotensin II receptors and PKC isoforms by glucose in rat mesangial cells.

It has been shown that glomerular angiotensin II (ANG II) receptors are downregulated and protein kinase C (PKC) is activated under diabetic conditions. We, therefore, investigated ANG II receptor and PKC isoform regulation in glomerular mesangial cells (MCs) under normal and elevated glucose concentrations. MCs were isolated from collagenase-treated rat glomeruli and cultured in medium containing normal or high glucose concentrations (5.5 and 25.0 mM, respectively). Competitive binding experiments were performed using the ANG II antagonists losartan and PD-123319, and PKC analysis was conducted by Western blotting. Competitive binding studies showed that the AT1 receptor was the only ANG II receptor detected on MCs grown to either subconfluence or confluence under either glucose concentration. AT1 receptor density was significantly downregulated in cells grown to confluence in high-glucose medium. Furthermore, elevated glucose concentration enhanced the presence of all MC PKC isoforms. In addition, PKCbeta, PKCgamma and PKCepsilon were translocated only in cells cultured in elevated glucose concentrations following 1-min stimulation by ANG II, whereas PKCalpha, PKCtheta, and PKClambda were translocated by ANG II only in cells grown in normal glucose. Moreover, no changes in the translocation of PKCdelta, PKCiota, PKCzeta, and PKCmu were detected in response to ANG II stimulation under euglycemic conditions. We conclude that MCs grown in high glucose concentration show altered ANG II receptor regulation as well as PKC isoform translocation compared with cells grown in normal glucose concentration.

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1998

Vasoactive peptide receptors in the rat kidney.

The kidney is composed of different complex structures regulating--among others--renal blood flow and glomerular filtration rate. Several vasoactive peptide systems are involved in that regulation, including atrial natriuretic peptides, the renin-angiotensin system, endothelin and their respective receptors. In this review, we will briefly describe the characteristics, location and regulation of these receptors in the rat kidney.

Animals↗

PubMed1997

Modulation of renal glomerular angiotensin II receptors by ace inhibition and AT1 receptor antagonism.

Angiotensin-converting enzyme inhibitors (ACE-I) and specific nonpeptide angiotensin II (ANG II) receptor antagonists have been used extensively to treat a variety of cardiovascular disorders in experimental animals and humans. Despite their widespread use, only a limited amount of data has been published regarding the effect that renin-angiotensin system (RAS) blockade may have on ANG II receptors, and very often this information is contradictory. The present study was designed to investigate whether changes in plasma ANG II levels induced by RAS blockade could alter glomerular ANG II receptor characteristics. Captopril was employed as an ACE-I with losartan and TCV-116, two AT1 receptor antagonists of different chemical structure. Two experimental protocols were established. Protocol 1 contained 3 experimental groups: controls (Sprague-Dawley rats, 250-300 g BW), and animals treated with either captopril (0.5 g/l via drinking water) or losartan (10 mg/kg BW p.o.). In protocol 2, the animals were treated as in protocol 1 except that losartan was replaced by TCV-116 (1 mg/kg BW p.o.). At the end of treatment (3 days), all groups were killed by decapitation, blood was collected for plasma renin activity (PRA) measurement, and hearts and kidneys were excised. ANG II receptors were assessed by radioligand binding assays on membrane preparations of purified glomeruli, by displacement of 125I-[Sar1, Ile8]-ANG II with specific nonpeptide antagonists of AT1 (losartan) and AT2 (PD 123319) receptor subtypes. RAS blockade by either ACE-I or AT1 antagonists increased PRA. The binding assays showed that renal glomeruli from treated rats and controls expressed a single population (AT1) of ANG II receptors. The density of glomerular AT1 receptors was not modulated by captopril, but was significantly lower in animals treated with either losartan (Bmax: 854 +/- 169 vs. 379 +/- 79 fmol/mg protein and Kd: 59 +/- 6 vs. 45 +/- 6 nM for controls and losartan, respectively) or TCV-116 (480 +/- 72 vs. 188 +/- 16 fmol/mg protein and Kd: 45 +/- 9 vs. 37 +/- 18 nM for controls and TCV-116, respectively) than in their controls. No changes in receptor affinity (Kd) were detected. Previous membrane "acid-wash" did not modify the results. We conclude that short-term RAS blockade by AT1 antagonists, but not by ACE-I, induces true downregulation of renal glomerular ANG II receptors. No AT2 receptor subtype was detected.

Angiotensin II↗

PubMed1997

Renal angiotensin II receptor regulation in two-kidney, one clip hypertensive rats: effect of ACE inhibition.

Local renal and plasma renin-angiotensin systems (RAS) both play an important role in blood pressure regulation during the development of two-kidney, one clip Goldblatt hypertension (2K1C) through their vasoactive component, angiotensin II (Ang II). Our goal was to characterize glomerular and preglomerular vascular Ang II receptors during the different stages of development of hypertension in 2K1C rats (2-, 4-, 8-, and 16-weeks postoperative) using Ang II antagonists [Sar1,Ile8]-Ang II, losartan, and PD 123319 and their regulation after angiotensin-converting enzyme (ACE) inhibition by captopril. Competitive binding studies showed that the only Ang II receptor detected on both glomeruli and preglomerular vessels of all groups (2-, 4-, 8-, and 16-week 2K1C rats, control rats, and captopril-treated rats) was the Ang II type 1 receptor (AT1). Vascular AT1 receptor density (Bmax) was significantly lower in only the 16-week 2K1C group, whereas glomerular Bmax was significantly lower in 2K1C rats at 2-, 4-, and 8-weeks. Vascular and glomerular receptor densities were both significantly higher in captopril-treated rats than in nontreated rats. We therefore conclude that in 2K1C rats, Ang II receptors on preglomerular vessels and glomeruli are regulated differentially during the development of hypertension and after ACE inhibition. Our results suggest that glomerular Ang II receptors are regulated by systemic plasma Ang II levels, whereas vascular Ang II receptors are not. However, when renal and systemic RASs are both blocked, these receptors are upregulated but are no longer differentially regulated.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

An artificial intelligence program for the radiologic diagnosis of brain lesions.

A software program has been developed that uses a frame-based expert system for differential diagnosis in neuroradiology. A frame-based expert system is used to store the magnetic resonance (MR) and computed tomographic (CT) imaging characteristics of over 100 known brain disorders in object-like entities. The frames are organized in a hierarchic structure in which lower order frames inherit attributes from higher order frames, with the highest frame containing information that applies to all the other frames. Program execution follows a consultation paradigm with a dynamic database. A decision tree menu provides a user-friendly interface with which to navigate through the network, based on features of the lesion as depicted on MR and CT images. The system can provide a differential diagnosis based on the MR imaging findings alone with information criteria including the signal intensity of the lesion on T1- and T2-weighted images, the location of the lesion, and the presence or absence of mass effect. The differential diagnosis may be further refined by adding CT-related information, including CT attenuation and the presence or absence of calcification and contrast enhancement.

Brain↗

PubMed1996

Differential regulation of renal glomerular and preglomerular vascular angiotensin II receptors.

The activity of the renin-angiotensin system (RAS) can be influenced by sodium intake and angiotensin II (ANG II) infusion. It has been shown that ANG II can regulate the density of its receptors. Therefore, we investigated the regulation of glomerular and preglomerular vascular ANG II receptors by changes in RAS activity. Sprague-Dawley rats were fed a low- or high-sodium diet or were infused with nonpressor or pressor doses of ANG II for 7 days. ANG II receptor characteristics were determined by radioligand binding assays with use of ANG II antagonists losartan and PD-123319. AT1 was the only receptor type found in membrane preparations from all groups. Glomerular ANG II receptor characteristics in all groups were unchanged compared with their controls, whereas vascular receptor density was significantly downregulated by sodium restriction. We conclude that glomerular and preglomerular vascular ANG II receptors are differentially regulated such that AT1 receptors in preglomerular vessels can be regulated by changes in endogenous RAS. ANG II infusion did not induce any modification of either glomerular or vascular AT1 receptors, suggesting a predominant role of the endogenous local renal RAS.

Angiotensin II↗

PubMed1995

A semantic network model for the medical record of a rheumatology clinic.

For the development of a rheumatology information system, a medical data dictionary was developed that supports all phases of software development. In the design phase, the medical expert described his clinical environment and the rheumatology medical record in a semantic network structure. Causal relationships between different items of the medical record (e.g., a problem may be related to an adverse drug event caused by a particular drug) are also represented in the semantic network and transferred into referential integrity constraints of the patient database. Furthermore, by also integrating the domain management as a feature of the medical data dictionary, the elementary attributes of the medical record and the associated lists of valid attribute entries have also been defined within the semantic network. This structure allowed the automatic generation of data entry screens, thus making the clinical applications as independent from any hardcoded program module as possible.

Algorithms↗

PubMed1990