Deletion of AT receptors selectively in the proximal tubules of the kidney alters the hypotensive and natriuretic response to atrial natriuretic peptide via NPR/cGMP/NO signaling.

In the proximal tubules of the kidney, angiotensin II (ANG II) binds and activates ANG II type 1 (AT) receptors to stimulate proximal tubule Na reabsorption, whereas atrial natriuretic peptide (ANP) binds and activates natriuretic peptide receptors (NPR) to inhibit ANG II-induced proximal tubule Na reabsorption. These two vasoactive systems play important counteracting roles to control Na reabsorption in the proximal tubules and help maintain blood pressure homeostasis. However, how AT and NPR receptors interact in the proximal tubules and whether natriuretic effects of NPR receptor activation by ANP may be potentiated by deletion of AT (AT) receptors selectively in the proximal tubules have not been studied previously.

Sex differences in the renin-angiotensin-aldosterone system and its roles in hypertension, cardiovascular, and kidney diseases.

Cardiovascular disease is a pathology that exhibits well-researched biological sex differences, making it possible for physicians to tailor preventative and therapeutic approaches for various diseases. Hypertension, which is defined as blood pressure greater than 130/80 mmHg, is the primary risk factor for developing coronary artery disease, stroke, and renal failure. Approximately 48% of American men and 43% of American women suffer from hypertension.

Genetic Deletion of AT Receptor or Na/H Exchanger 3 Selectively in the Proximal Tubules of the Kidney Attenuates Two-Kidney, One-Clip Goldblatt Hypertension in Mice.

The roles of angiotensin II (Ang II) AT1 (AT1a) receptors and its downstream target Na+/H+ exchanger 3 (NHE3) in the proximal tubules in the development of two-kidney, 1-clip (2K1C) Goldblatt hypertension have not been investigated previously. The present study tested the hypothesis that deletion of the AT1a receptor or NHE3 selectively in the proximal tubules of the kidney attenuates the development of 2K1C hypertension using novel mouse models with proximal tubule-specific deletion of AT1a receptors or NHE3. 2K1C Goldblatt hypertension was induced by placing a silver clip (0.

Clinical outcomes of implant-supported monolithic zirconia crowns and fixed partial dentures: A systematic review.

Purpose: To determine the survival rates of implant-supported monolithic zirconia crowns and fixed partial dentures (FPD).

Material And Methods: An electronic search for articles in the English language literature published from January 1, 2001 to September 17, 2021 was performed using PubMed, Scopus, and CENTRAL search engines. After applying predetermined inclusion and exclusion criteria, the definitive list of selected articles was used for calculating the interval survival rate (ISR) and cumulative survival rate (CSR).

Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.

The concept of local formation of angiotensin II in the kidney has changed over the last 10-15 years. Local synthesis of angiotensinogen in the proximal tubule has been proposed, combined with prorenin synthesis in the collecting duct. Binding of prorenin via the so-called (pro)renin receptor has been introduced, as well as megalin-mediated uptake of filtered plasma-derived renin-angiotensin system (RAS) components.

The Na/H Exchanger 3 in the Intestines and the Proximal Tubule of the Kidney: Localization, Physiological Function, and Key Roles in Angiotensin II-Induced Hypertension.

The sodium (Na)/hydrogen (H) exchanger 3 (NHE3) is one of the most important Na/H antiporters in the small intestines of the gastrointestinal tract and the proximal tubules of the kidney. The roles of NHE3 in the regulation of intracellular pH and acid-base balance have been well established in cellular physiology using techniques. Localized primarily on the apical membranes in small intestines and proximal tubules, the key action of NHE3 is to facilitate the entry of luminal Na and the extrusion of intracellular H from intestinal and proximal tubule tubular epithelial cells.

Angiotensin II and AT Receptors in the Proximal Tubules of the Kidney: New Roles in Blood Pressure Control and Hypertension.

Contrary to public perception, hypertension remains one of the most important public health problems in the United States, affecting 46% of adults with increased risk for heart attack, stroke, and kidney diseases. The mechanisms underlying poorly controlled hypertension remain incompletely understood. Recent development in the approach to study gain or loss of function of a particular gene has significantly helped advance our new insights into the role of proximal tubule angiotensin II (Ang II) and its AT (AT) receptors in basal blood pressure control and the development of Ang II-induced hypertension.

A technique for improved gingival esthetics on complete arch implant-supported acrylic resin prototype prosthesis.

An important step during the workflow of complete arch fixed implant-supported prostheses is the fabrication of an acrylic resin prototype prosthesis so that the patient can visualize the definitive treatment outcome or to be used as an interim prosthesis. The prototype prosthesis is typically designed digitally as a single file and is produced by milling from a solid block of white-colored prepolymerized acrylic resin. A common challenge in fabricating a resin-based prototype prosthesis is reproducing the natural appearance of the gingival architecture in gingiva-colored material.

Intratubular, Intracellular, and Mitochondrial Angiotensin II/AT (AT1a) Receptor/NHE3 Signaling Plays a Critical Role in Angiotensin II-Induced Hypertension and Kidney Injury.

Hypertension is well recognized to be the most important risk factor for cardiovascular diseases, stroke, and end-stage kidney failure. A quarter of the world's adult populations and 46% of the US adults develop hypertension and currently require antihypertensive treatments. Only 50% of hypertensive patients are responsive to current antihypertensive drugs, whereas remaining patients may continue to develop cardiovascular, stroke, and kidney diseases.

Sex differences in angiotensin II-induced hypertension and kidney injury: role of AT1a receptors in the proximal tubule of the kidney.

In the present study, we tested the hypothesis that there are significant sex differences in angiotensin II (Ang II)-induced hypertension and kidney injury using male and female wildtype (WT) and proximal tubule-specific AT1a receptor knockout mice (PT-Agtr1a-/-). Twelve groups (n=8-12 per group) of adult male and female WT and PT-Agtr1a-/- mice were infused with a pressor dose of Ang II via osmotic minipump for 2 weeks (1.5 mg/kg/day, i.

New Insights into the Critical Importance of Intratubular Na/H Exchanger 3 and Its Potential Therapeutic Implications in Hypertension.

Purpose Of Review: The sodium (Na) and hydrogen (H) exchanger 3 (NHE3), known as solute carrier family 9 member 3 (SLC9A3), mediates active transcellular Na and bicarbonate reabsorption in the small intestine of the gut and proximal tubules of the kidney. The purpose of this article is to review and discuss recent findings on the critical roles of intestinal and proximal tubule NHE3 in maintaining basal blood pressure (BP) homeostasis and their potential therapeutic implications in the development of angiotensin II (Ang II)-dependent hypertension.

Recent Findings: Recently, our and other laboratories have generated or used novel genetically modified mouse models with whole-body, kidney-specific, or proximal tubule-specific deletion of NHE3 to determine the critical roles and underlying mechanisms of NHE3 in maintaining basal BP homeostasis and the development of Ang II-induced hypertension at the whole-body, kidney, or proximal tubule levels.

Design and evaluation of a custom 50K Infinium SNP array for egg-type chickens.

With the development of molecular genetics and high-throughput sequencing technology, genotyping arrays consisting of large numbers of SNP have raised great interest in animal and plant research. However, the application of commercial chicken 600K SNP arrays has varied in different populations of egg-type chickens. Moreover, their genotyping cost is too high for large-scale population applications.

Proximal Tubule-Specific Deletion of Angiotensin II Type 1a Receptors in the Kidney Attenuates Circulating and Intratubular Angiotensin II-Induced Hypertension in PT- Mice.

[Figure: see text].

A novel mutation causes autosomal dominant cataract: A report from a Chinese family.

Purpose: This study aimed to examine pathogenic mutation within one Chinese family of five-generations suffering from autosomal dominant cataract.

Methods: Next-generation sequencing and Sanger sequencing were used to find the pathogenic variants.

Results: A rare mutation, c.

Evidence for a Physiological Mitochondrial Angiotensin II System in the Kidney Proximal Tubules: Novel Roles of Mitochondrial Ang II/AT/O and Ang II/AT/NO Signaling.

The present study tested the hypotheses that overexpression of an intracellular Ang II (angiotensin II) fusion protein, mito-ECFP/Ang II, selectively in the mitochondria of mouse proximal tubule cells induces mitochondrial oxidative and glycolytic responses and elevates blood pressure via the Ang II/AT receptor/superoxide/NHE3 (the Na/H exchanger 3)-dependent mechanisms. A PT-selective, mitochondria-targeting adenoviral construct encoding Ad-sglt2-mito-ECFP/Ang II was used to test the hypotheses. The expression of mito-ECFP/Ang II was colocalized primarily with Mito-Tracker Red FM in mouse PT cells or with TMRM in kidney PTs.

[Genome-wide identification, phylogenetic analysis and expression profiling of the MKK gene family in ].

Mitogen-activated protein kinase kinase (MAPKK or MKK) is an important component of the MAPK cascade, which plays important roles in plant growth and development as well as in various stress responses. At present, the MKK gene family has been identified in a variety of plants, but there has been no systematic study in Cruciferous plant . To explore the evolution and function of the MKK gene family in , 16 genes were identified from the genome by genome-wide analysis, and they were distributed on 10 chromosomes of .

Progresses in the plant 3D chromatin architecture.

Chromatin architecture involves the patterns of chromatin coiling and packing as well as the mutual relative allocations of different chromatins. Besides the canonical microscopic observations, the chromatin architectural capture techniques, including the Hi-C and ChIA-PET, have been widely applied in characterization of chromatin architecture in various plant and animal model species, in which chromatin architectural features, such as the chromosome territory, compartment A/B, topological associated domains (TADs) and chromatin loops, were defined. As for the studies in plant species, replying on the two techniques above (with differences in experimental techniques and data structures), scientists have compared the variation of specific chromatin architecture features across species and/or in different cell types of the same plant species, besides detailed analyses in each individual model.

Proximal Tubule-Specific Deletion of the NHE3 (Na/H Exchanger 3) in the Kidney Attenuates Ang II (Angiotensin II)-Induced Hypertension in Mice.

The present study directly tested the hypothesis that the NHE3 (Na/H exchanger 3) in the proximal tubules of the kidney is required for the development of Ang II (angiotensin II)-induced hypertension using PT-Nhe3 (proximal tubule-specific NHE3 knockout) mice. Specifically, PT-Nhe3 mice were generated using the SGLT2-Cre/Nhe3 approach, whereas Ang II-induced hypertension was studied in 12 groups (n=5-12 per group) of adult male and female wild-type (WT) and PT-Nhe3 mice. Under basal conditions, systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were significantly lower in male and female PT-Nhe3 than WT mice (P<0.

Angiotensin III/AT Receptor/NHE3 Signaling Pathway in the Proximal Tubules of the Kidney: A Novel Natriuretic and Antihypertensive Mechanism in Hypertension.

See Article Kemp et al.

Genetic and genomic evidence for an important role of the Na/H exchanger 3 in blood pressure regulation and angiotensin II-induced hypertension.

The sodium (Na)/hydrogen (H) exchanger 3 (NHE3) and sodium-potassium adenosine triphosphatase (Na/K-ATPase) are two of the most important Na transporters in the proximal tubules of the kidney. On the apical membrane side, NHE3 primarily mediates the entry of Na into and the exit of H from the proximal tubules, directly and indirectly being responsible for reabsorbing ~50% of filtered Na in the proximal tubules of the kidney. On the basolateral membrane side, Na/K-ATPase serves as a powerful engine driving Na out of, while pumping K into the proximal tubules against their concentration gradients.

Proximal Tubule-Specific Deletion of the NHE3 (Na/H Exchanger 3) Promotes the Pressure-Natriuresis Response and Lowers Blood Pressure in Mice.

The present study directly tested the hypothesis that deletion of the NHE3 (Na/H exchanger 3) selectively in the proximal tubules of the kidney lowers basal blood pressure by increasing the pressure-natriuresis response in mice. Adult male and female, age-matched wild-type (WT) littermates and proximal tubule-specific NHE3 knockout mice (PT- Nhe3; n=6-16 per group) were studied for (1) basal phenotypes of electrolytes and pH, blood pressure, and kidney function; (2) the pressure-natriuresis response using the mesenteric, celiac, and abdominal arterial occlusion technique; and (3) the natriuretic responses to acute saline expansion (0.9% NaCl, 10% body weight, intraperitoneal) or 2-week of 2% NaCl diet.

Intratubular and intracellular renin-angiotensin system in the kidney: a unifying perspective in blood pressure control.

The renin-angiotensin system (RAS) is widely recognized as one of the most important vasoactive hormonal systems in the physiological regulation of blood pressure and the development of hypertension. This recognition is derived from, and supported by, extensive molecular, cellular, genetic, and pharmacological studies on the circulating (tissue-to-tissue), paracrine (cell-to-cell), and intracrine (intracellular, mitochondrial, nuclear) RAS during last several decades. Now, it is widely accepted that circulating and local RAS may act independently or interactively, to regulate sympathetic activity, systemic and renal hemodynamics, body salt and fluid balance, and blood pressure homeostasis.

The vasoprotective axes of the renin-angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases.

The renin-angiotensin system (RAS) is undisputedly one of the most prominent endocrine (tissue-to-tissue), paracrine (cell-to-cell) and intracrine (intracellular/nuclear) vasoactive systems in the physiological regulation of neural, cardiovascular, blood pressure, and kidney function. The importance of the RAS in the development and pathogenesis of cardiovascular, hypertensive and kidney diseases has now been firmly established in clinical trials and practice using renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors, type 1 (AT) angiotensin II (ANG II) receptor blockers (ARBs), or aldosterone receptor antagonists as major therapeutic drugs. The major mechanisms of actions for these RAS inhibitors or receptor blockers are mediated primarily by blocking the detrimental effects of the classic angiotensinogen/renin/ACE/ANG II/AT/aldosterone axis.

Luminal ANG II is internalized as a complex with ATR/ATR heterodimers to target endoplasmic reticulum in LLC-PK cells.

ANG II has many biological effects in renal physiology, particularly in Ca handling in the regulation of fluid and solute reabsorption. It involves the systemic endocrine renin-angiotensin system (RAS), but tissue and intracrine ANG II are also known. We have shown that ANG II induces heterodimerization of its AT and AT receptors (ATR and ATR) to stimulate sarco(endo)plasmic reticulum Ca-ATPase (SERCA) activity.