Angiotensin II/Angiotensin (1-7) ratio and 24-h blood pressure throughout the menstrual cycle and in women using oral contraceptives.

Background: Women using oral contraceptives have higher ambulatory blood pressures (BPs) than other women. We sought to learn whether this was associated with an alteration in the balance of angiotensin II (Ang)/Ang (1-7) and whether this ratio and BP remained constant throughout the menstrual cycle.

Method: In total, 30 (15 ovulatory, 15 taking oral contraceptives) healthy, normotensive women aged 18-30 years were studied.

Vasoprotective and atheroprotective effects of angiotensin (1-7) in apolipoprotein E-deficient mice.

Objective: To evaluate the effectiveness of long-term angiotensin (Ang) (1-7) treatment to inhibit the progression of atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice.

Methods And Results: Ang (1-7) is a heptapeptide fragment that has been proposed to counterregulate the Ang II proatherogenic effects. The effect of long-term 4-week Ang (1-7) treatment on both inhibition of atherosclerotic lesion development and improvement of endothelial function was examined in apolipoprotein E(-/-) mice that had been fed an atherogenic high-fat (21%) diet for 16 weeks.

Portal pressure responses and angiotensin peptide production in rat liver are determined by relative activity of ACE and ACE2.

Angiotensin converting enzyme (ACE) 2 activity and angiotensin-(1-7) [Ang-(1-7)] levels are increased in experimental cirrhosis; however, the pathways of hepatic Ang-(1-7) production have not been studied. This study investigated the role of ACE2, ACE, and neutral endopeptidase (NEP) in the hepatic formation of Ang-(1-7) from angiotensin I (Ang I) and Ang II and their effects on portal resistance. Ang I or Ang II were administered to rat bile duct ligated (BDL) and control livers alone and in combination with the ACE inhibitor lisinopril, the ACE and NEP inhibitor omapatrilat, or the ACE2 inhibitor MLN4760 (n = 5 per group).

Angiotensin-(1-7), an alternative metabolite of the renin-angiotensin system, is up-regulated in human liver disease and has antifibrotic activity in the bile-duct-ligated rat.

Ang-(1-7) (angiotensin-1-7), a peptide product of the recently described ACE (angiotensin-converting enzyme) homologue ACE2, opposes the harmful actions of AngII (angiotensin II) in cardiovascular tissues, but its role in liver disease is unknown. The aim of the present study was to assess plasma levels of Ang-(1-7) in human liver disease and determine its effects in experimental liver fibrosis. Angiotensin peptide levels were measured in cirrhotic and non-cirrhotic patients with hepatitis C.

Angiotensin converting enzyme 2 (ACE2) activity in fetal calf serum: implications for cell culture research.

Cell culture experiments often employ the use of culture media that contain fetal calf serum (FCS). The angiotensin peptides angiotensin II and angiotensin 1-7 have opposing effects with angiotensin converting enzyme 2 (ACE2) being the enzyme predominantly responsible for generating angiotensin 1-7 from angiotensin II. The effect of FCS on angiotensin peptides has not previously been described.

Tracing neurotrophin-3 diffusion and uptake in the guinea pig cochlea.

Neurotrophin therapy in the cochlea can potentially slow or reverse the degeneration of the auditory nerve that occurs during progressive deafness. Studies were performed to trace the diffusion and uptake of neurotrophin-3 (NT-3) following infusion into the cochlea. NT-3 labeled with (125)I or coated onto fluorescent microspheres was introduced into the basal turn of normal hearing and deafened guinea pig cochleae via a single slow-rate injection.

Novel hexad repeats conserved in a putative transporter with restricted expression in cell types associated with growth, calcium exchange and homeostasis.

A transport protein is described with 12 transmembrane spans. Within the cytoplasmic amino-terminal domain, several novel hexad repeats are conserved in human, mouse, rat and pig, four to six of which had the canonical form PS_S_H(+). In the carboxyl-terminal domain, a polyglutamate sequence (5-8) is conserved.

Differential tissue and enzyme inhibitory effects of the vasopeptidase inhibitor omapatrilat in the rat.

Vasopeptidase inhibitors simultaneously inhibit angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The present study characterized the tissue distributions of ACE and NEP, and assessed the effects of the vasopeptidase inhibitor omapatrilat on ACE and NEP in rat tissues. In vivo ACE and NEP inhibition was studied by in vitro autoradiography and using the ACE inhibitor radioligand (125)I-MK351A and the NEP inhibitor radioligand (125)I-RB104 in rats that received oral omapatrilat (40 mg x day(-1) x kg(-1)) for 3 days.

Calcitonin receptor isoforms expressed in the developing rat kidney.

Background: Development in the metanephric-kidney transition period involves the precise expression of paracrine and autocrine events in an ordered spatio-temporal manner. Expression of these molecular events is tightly controlled and includes positive and negative growth factors and cognate receptors within close proximity in developing structures in the expanding renal cortex and medulla. The expression of calcitonin receptor (CTR) isoforms C1a and C1b in this context has not previously been described.

Renal expression of angiotensin receptors in long-term diabetes and the effects of angiotensin type 1 receptor blockade.

Objective: The aims of this study were to assess the renal expression of angiotensin type 1 (AT1) and type 2 (AT2) receptors in diabetic spontaneously hypertensive rats (SHR) and the effect of AT1 receptor blockade on the expression of these receptors.

Design: Diabetes was induced by injection of streptozotocin in SHRs. Irbesartan, an AT1 receptor antagonist, was given to diabetic SHRs for 32 weeks (15 mg/kg per day, n = 10).

A low-sodium diet potentiates the effects of losartan in type 2 diabetes.

Objective: Diabetic subjects have a high prevalence of hypertension, increased total body exchangeable sodium levels, and an impaired ability to excrete a sodium load. This study assessed the effect of dietary sodium restriction on the efficacy of losartan in hypertensive subjects with type 2 diabetes and albumin excretion rates of 10-200 microg/min.

Research Design And Methods: In this study, 20 subjects were randomized to losartan 50 mg/day (n = 10) or placebo (n = 10).

Combined inhibition of neutral endopeptidase with angiotensin converting enzyme or endothelin converting enzyme in experimental diabetes.

Objective: The effects of combined inhibition of neutral endopeptidase (NEP) with either angiotensin-converting enzyme (ACE), or endothelin-converting enzyme (ECE) on blood pressure, urinary albumin excretion and heart weight were explored in experimental diabetes.

Design: Streptozotocin-induced diabetic Sprague-Dawley rats were treated with vehicle, the NEP/ACE inhibitor S 21402, the NEP/ECE inhibitor CGS 26303, the NEP inhibitor SCH 42495, the ACE inhibitor captopril or the endothelin receptor antagonist bosentan for 4 weeks.

Methods: Blood pressure was measured by tail-cuff method and radiotelemetry.

Evidence for activation of the renin-angiotensin system in the human prostate: increased angiotensin II and reduced AT(1) receptor expression in benign prostatic hyperplasia.

The expression and cellular localization of angiotensin II (Ang II) and AT(1) receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT(1) receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.

Localization of angiotensin-converting enzyme in the human prostate: pathological expression in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common hyperplastic disease in man and it is characterized by increased cellular growth (stromal and epithelial hyperplasia) and enhanced local sympathetic tone, both of which are known to be augmented by activation of the renin-angiotensin system (RAS) in other tissues. Angiotensin-converting enzyme (ACE) is an integral component of the RAS that is responsible for the production of the active peptide angiotensin II from the inactive precursor angiotensin I. The present study was undertaken to map the anatomical localization of ACE protein and messenger ribonucleic acid (mRNA) in the normal human prostate and to establish whether their expression is pathologically altered in BPH.

Angiotensin AT(4) receptors in the normal human prostate and benign prostatic hyperplasia.

The cellular localisation and expression of angiotensin AT(4) receptors was examined in the normal human prostate and benign prostatic hyperplasia (BPH) by quantitative in vitro autoradiography using [(125)I]-Ang IV. In the normal human prostate, AT(4) receptors were localised to the glandular epithelium. Interestingly, specific AT(4) receptor binding was significantly reduced in BPH compared to the normal prostate, as quantitated macroscopically (normal: 5038+/-476 dpm/mm(2), n=6 vs BPH: 2701+/-176 dpm/mm(2), n=6, P<0.

Effect of glycerol-induced hyperhydration on thermoregulation and metabolism during exercise in heat.

This study examined the effect of glycerol ingestion on fluid homeostasis, thermoregulation, and metabolism during rest and exercise. Six endurance-trained men ingested either 1 g glycerol in 20 ml H2O x kg(-1) body weight (bw) (GLY) or 20 ml H2O x kg(-1) bw (CON) in a randomized double-blind fashion, 120 min prior to undertaking 90 min of steady state cycle exercise (SS) at 98% of lactate threshold in dry heat (35 degrees C, 30% RH), with ingestion of CHO-electrolyte beverage (6% CHO) at 15-min intervals. A 15-min cycle, where performance was quantified in kJ, followed (PC).

Vascular expression of angiotensin type 2 receptor in the adult rat: influence of angiotensin II infusion.

Objective: The aim of this study was to investigate the relative role of the angiotensin type 1 (AT1) and type 2 (AT2) receptors in mediating angiotensin II-induced regulation of AT2 receptor in mesenteric artery.

Design: Sprague-Dawley rats were infused with either angiotensin II or vehicle for 14 days at a dose of 58.3 ng/min.

In-vitro and in-vivo inhibition of rat neutral endopeptidase and angiotensin converting enzyme with the vasopeptidase inhibitor gemopatrilat.

Objectives: Vasopeptidase inhibitors are single molecules that simultaneously inhibit neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE). The aim of this study was to characterize in-vitro and in-vivo inhibition of NEP and ACE in the rat with the vasopeptidase inhibitor gemopatrilat.

Design And Methods: In-vitro NEP and ACE inhibition was studied by radioinhibitory binding assay using rat renal membranes and the specific NEP inhibitor radioligand 125I-RB104 and the specific ACE inhibitor radioligand 125I-MK351A, respectively (n = 3 per curve).

Angiotensin II binding to renomedullary interstitial cells is regulated by osmolality.

Angiotensin II (Ang II) AT(1A) receptors are localized to renomedullary interstitial cells (RMIC) in the inner stripe of the outer medulla but not in the inner medulla. Thus, there seems to be a correlation between decreases in AT(1A) receptor binding to RMIC and increases in interstitial osmolality, suggesting that osmolality is important in determining Ang II binding to RMIC. Cultured RMIC were incubated in media of differing osmolalities (330, 630, 930, and 1230 mOsm/kg H(2)O).

Identification, distribution, and expression of angiotensin II receptors in the normal human prostate and benign prostatic hyperplasia.

The tissue distribution, cellular localization, and level of expression of angiotensin II (Ang II) receptors were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by in vitro autoradiography, immunohistochemistry, and radioligand binding studies. In the normal human prostate, Ang II receptors were of the AT(1) subtype and localized predominantly to periurethral stromal smooth muscle. The AT(1) receptor antagonist losartan totally displaced specific [(125)I]-[Sar(1),Ile(8)]Ang II binding, in a concentration-dependent manner, whereas the AT(2) receptor antagonist PD123319 was without effect.

Angiotensin type 2 receptor is expressed in the adult rat kidney and promotes cellular proliferation and apoptosis.

Background: Angiotensin II (Ang II) is associated with cell proliferation and apoptosis. The role of the angiotensin type 2 receptor (AT2R) in these processes remains controversial. Conventional radioligand binding of 125I-Sar1, Ile8 Ang II in adult kidney has failed to demonstrate the binding for the AT2R.

Comparative in vivo effects of irbesartan and losartan on angiotensin II receptor binding in the rat kidney following oral administration.

We examined the ability of the new non-peptide angiotensin II receptor antagonist irbesartan to inhibit AT(1) receptors in vivo in the rat kidney following oral administration, compared with the prototype drug losartan. Male Sprague-Dawley rats (250-300 g) were gavaged with either irbesartan or losartan at doses of 1, 3, 10, 30 or 100 mg/kg, or with corresponding vehicle. Rats were killed at 0, 1, 2, 8, or 24 h after drug administration, trunk blood was collected and the kidneys were removed.

In vivo inhibition of angiotensin receptors in the rat kidney by candesartan cilexetil: a comparison with losartan.

The present study examined the in vivo effects of candesartan cilexetil compared with losartan on angiotensin II (Ang II) receptor binding in the rat kidney after oral administration. Male Sprague-Dawley rats (250 to 300 g) were gavaged with candesartan cilexetil or losartan in doses of 0.1, 0.

O-glycosylation delays the clearance of human IGF-binding protein-6 from the circulation.

Objective: The actions of insulin-like growth factors (IGF-I and IGF-II) are modulated by a family of six structurally related, high-affinity binding proteins (IGFBPs 1-6). IGFBP-6, an O-linked glycoprotein, preferentially binds IGF-II and inhibits its actions. The aim of this study was to investigate whether O-glycosylation modulates the pharmacokinetics of IGFBP-6.

Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in experimental diabetes.

It has been suggested that the cytokine vascular endothelial growth factor (VEGF) has an important role in the pathogenesis of diabetic retinopathy, but its role in nephropathy has not been clearly demonstrated. Assessment of VEGF, 125I-VEGF binding, and vascular endothelial growth factor receptor-2 (VEGFR-2) in the kidney was performed after 3 and 32 weeks of streptozotocin-induced diabetes. Gene expression of both VEGF and VEGFR-2 was assessed by Northern blot analysis and the localization of the ligand and receptor was examined by in situ hybridization.