ABSTRACT
The abdominal wall can be treated as a whole physiological and functional entity which is composed of multiple anatomical structures and planes. Surgical approaches and technical details that required are diverse in different area. Indeed, the abdominal wall is confined by several anatomical boundaries which make these surgical planes separated. If one could dissect these boundaries, then separated spaces could be connected, establishing an ample retromuscular/preperitoneal space to accommodate the mesh of ventral hernia repair. The concept of totally visceral sac separation (TVS) is achieved. The TVS concept is a summary of diverse ventral hernia repair techniques. Since its initiation and spread, this technique has been widely accepted and implemented by domestic surgeons due to its outstanding performance. This treatise will review the relevant anatomy as well assurgical tricks by the authors that aid in performing TVS. Some of the details are more tricky and harder to understand, thus this in-depth description of the technique.
Subject(s)
Abdominal Wall , Hernia, Ventral , Laparoscopy , Humans , Surgical Mesh , Hernia, Ventral/surgery , Endoscopy , Abdominal Wall/surgery , Herniorrhaphy/methods , Laparoscopy/methodsABSTRACT
OBJECTIVES: To determine the risk of total knee replacement (TKR) for primary osteoarthritis (OA) associated with overweight/obesity in the Australian population. METHODS: This population-based study analyzed 191,723 cases of TKR collected by the Australian Orthopaedic Association National Joint Registry and population data from the Australian Bureau of Statistics. The time-trend change in incidence of TKR relating to BMI was assessed between 2015 and 2018. The influence of obesity on the incidence of TKR in different age and gender groups was determined. The population attributable fraction (PAF) was then calculated to estimate the effect of obesity reduction on TKR incidence. RESULTS: The greatest increase in incidence of TKR was seen in patients from obese class III. The incidence rate ratio for having a TKR for obesity class III was 28.683 at those aged 18-54 years but was 2.029 at those aged >75 years. Females in obesity class III were 1.7 times more likely to undergo TKR compared to similarly classified males. The PAFs of TKR associated with overweight or obesity was 35%, estimating 14,287 cases of TKR attributable to obesity in 2018. The proportion of TKRs could be reduced by 20% if overweight and obese population move down one category. CONCLUSIONS: Obesity has resulted in a significant increase in the incidence of TKR in the youngest population in Australia. The impact of obesity is greatest in the young and the female population. Effective strategies to reduce the national obese population could potentially reduce 35% of the TKR, with over 10,000 cases being avoided.
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Australia/epidemiology , Female , Humans , Incidence , Male , Obesity/complications , Obesity/epidemiology , Osteoarthritis, Knee/epidemiology , Osteoarthritis, Knee/etiology , Osteoarthritis, Knee/surgery , Overweight/complications , Overweight/epidemiologyABSTRACT
ABSTRACT: Objective To select and develop a SNP-STR multiplex amplification system with genetic markers compatible with current STR databases. To understand its genetic polymorphisms in Sichuan Han population and its application value in DNA mixture analysis. Methods Based on the STR genetic markers in commercial kits, SNPs adjacent to these STR markers were selected to be SNP-STR genetic markers. A SNP-STR multiplex amplification system with genetic markers based on allele-specific amplification was constructed using allele-specific amplification primers. The genetic polymorphism of the system in the Sichuan Han population was investigated and the efficiency of systems with different numbers of loci to detect the two individual DNA mixture samples was evaluated. Results An allele-specific multiplex amplification system constituted of 13 SNP-STR genetic markers was selected and constructed. In Sichuan Han population, the heterozygosity of each locus ranged from 0.76 to 0.88, and the combined discrimination power reached 0.999 999 999 999 999 968. In the analysis of the two individual DNA mixture samplesï¼ for single-locus amplification, the genotype of the minor components can still be detected when the mixture ratio reaches 1 000â¶1; for multiple loci multiplex amplification, the maximum mixture ratio can reach 500â¶1. As the number of loci in the system increased, the detection efficiency of the minor components in the DNA mixture decreased. Conclusion SNP-STR genetic markers have a higher polymorphism than STR. The multiplex amplification system made of SNP-STR genetic markers has a better analysis efficiency for mixed samples than traditional STR multiplex amplification system.
Subject(s)
DNA Fingerprinting , Polymorphism, Single Nucleotide , China , DNA Primers , Gene Frequency , Genetic Markers , Humans , Microsatellite Repeats , Polymerase Chain ReactionABSTRACT
Objective: To compare the effects of different types of anesthesia on postoperative cardiopulmonary complications in patients aged 80 years and above who received unilateral hip fracture surgery. Methods: The perioperative data of patients aged 80 and above who underwent unilateral hip fracture surgery in Peking Union Medical College Hospital from July 2009 to June 2014 were collected and grouped based on the types of anesthesia including general anesthesia, neuraxial anesthesia, and peripheral nerve block. Variables were analyzed including preoperative general conditions (age, sex, type of fracture, ASA physical status classification, preoperative cardiopulmonary complications), intraoperative conditions (type of surgical procedure, operative time, blood loss, total intraoperative fluid infusion), and postoperative conditions (length of hospital stay, postoperative hospital stay, ICU stay, postoperative newly developed cardiopulmonary complications, postoperative in-hospital death, hospitalization costs). The incidences of postoperative cardiopulmonary complications of each group were analyzed and compared. Results: A total of 219 cases were finally analyzed including general anesthesia (n=46), neuraxial anesthesia (n=90) and nerve block group (n=83). Fewer cases with preoperative pulmonary complications were noticed in general anesthesia group (15 cases, 32.6%) than in neuraxial anesthesia group (45 cases, 50%) and nerve block group (47 cases, 56.6%) (χ(2)=6.912, P=0.032). No statistical differences were found between groups regarding preoperative cardiovascular complications and other variables. There were no significant differences in postoperative cardiopulmonary complications. However, the cost of hospitalization was lower in neuraxial anesthesia group (45.6±21.4) thousand RMB and nerve block group (48.2±25.8) thousand RMB compared with general anesthesia group (56.3±21.6) thousand RMB, the difference was statistically significant(F=9.951, P=0.007). Conclusions: For elderly patients undergoing unilateral hip surgery, the type of anesthesia does not affect the incidence of postoperative cardiopulmonary complications. However, neuraxial anesthesia and nerve block may reduce the cost of hospitalization.
Subject(s)
Anesthesia, General , Hip Fractures , Aged, 80 and over , Humans , Nerve Block , Postoperative Complications , Retrospective Studies , Treatment OutcomeABSTRACT
A new carbonized pomelo peel biosorbent (MCPP) modified with nanoscale zero-valent iron (NZVI) and cetyl-trimethyl ammonium bromide was prepared and employed for the adsorption of molybdate (Mo(VI)) from aqueous solution. We investigated the effects of various conditions on Mo(VI) adsorption and evaluated the results based on adsorption kinetics models and isotherm equations. The kinetic data fitted to the pseudo-second-order model. The Langmuir model best described the adsorption of Mo(VI) on MCPP. The values of changes in Gibbs free energy, standard enthalpy, and standard entropy revealed that the adsorption process was feasible, spontaneous and endothermal. X-ray diffraction, Fourier transform infrared and X-ray photoelectron spectroscopy measurements suggested that Mo(VI) adsorption occurred via both the reduction and surface adsorption. Thus, biochar, prepared from fruit residue, can be applied to remove Mo(VI) from aqueous solutions. More importantly, our results provide a sustainable approach for Mo(VI) removal from wastewater by means of functional modification.
Subject(s)
Bromides/chemistry , Charcoal , Iron/chemistry , Metal Nanoparticles/chemistry , Molybdenum/chemistry , Quaternary Ammonium Compounds/chemistry , Adsorption , Cetrimonium , Cetrimonium Compounds , Chromium/chemistry , Kinetics , Solutions , Wastewater/chemistry , Water Pollutants, Chemical/chemistry , X-Ray DiffractionABSTRACT
Enterovirus A-71 (EV-A71) may be fatal, but the natural history, symptoms, and signs are poorly understood. This study aimed to examine the natural history of fatal EV-A71 infection and to identify the symptoms and signs of early warning of deterioration. This was a clinical observational study of fatal cases of EV-A71 infection treated at five Chinese hospitals between 1 January 2010 and 31 December 2012. We recorded and analysed 91 manifestations of EV-A71 infection in order to identify early prognosis indicators. There were 54 fatal cases. Median age was 21.5 months (Q1-Q3: 12-36). The median duration from onset to death was 78.5 h (range, 6 to 432). The multilayer perceptron analysis showed that ataxia respiratory, ultrahyperpyrexia, excessive tachycardia, refractory shock, absent pharyngeal reflex, irregular respiratory rhythm, hyperventilation, deep coma, pulmonary oedema and/or haemorrhage, excessive hypertension, tachycardia, somnolence, CRT extension, fatigue or sleepiness and age were associated with death. Autopsy findings (n = 2) showed neuronal necrosis, softening, perivascular cuffing, colloid and neuronophagia phenomenon in the brainstem. The fatal cases of enterovirus A71 had neurologic involvement, even at the early stage. Direct virus invasion through the neural pathway and subsequent brainstem damage might explain the rapid progression to death.
Subject(s)
Central Nervous System Infections/mortality , Central Nervous System Infections/pathology , Enterovirus A, Human/isolation & purification , Enterovirus Infections/mortality , Enterovirus Infections/pathology , Adolescent , Central Nervous System Infections/epidemiology , Child , Child, Preschool , China/epidemiology , Disease Progression , Enterovirus Infections/epidemiology , Female , Humans , Infant , Male , Prognosis , Time FactorsABSTRACT
Objective: The growing body of literature showed a link between uric acid and pulmonary hypertension (PH), but the impact of hyperuremia on outcome of patients with PH has not been well defined. Therefore, the present study was performed to analyze the impact of uric acid on outcome of PH patients. Methods: One hundred seventy-three PH patients (112 females, mean age 38 years old), who were hospitalized in our department between January 2010 and December 2015, were included in our study, the PH diagnosis was made based on right heart catheterization examination result (mean pulmonary artery pressure≥25 mmHg(1 mmHg=0.133 kPa)). PH patients were divided into mild to moderate PH group (Rp/Rs≤0.6, n=97) and severe PH group (Rp/Rs>0.6, n=76). Fifty-one patients (33 females, mean age 45 years old) without PH based on right heart catheterization were included as control subjects. All participants were followed up for a median of 24 months(6-71 months). Clinical endpoints were defined as cardiogenic death or heart-and-lung transplantation. Results: Uric acid was positively correlated with pulmonary vascular resistance(r=0.398, P<0.01), systemic vascular resistance(r=0.244, P<0.01) and mean right atrial pressure (r=0.26, P<0.01), and was negatively correlated with cardiac index(r=-0.278, P<0.01)and mixed venous oxygen saturation (r=-0.322, P<0.01)in PH patients. Serum uric acid level was significantly higher in patients with severe PH than in patients with mild-to-moderate PH and the control subjects (both P<0.05). According to the receiver operating characteristic curve (ROC), 425.5 µmol/L was found to be the best cut-off value of serum uric acid level to predict the outcome of PH patients (sensitivity 50%, specificity 72%). During follow-up, patients with higher level of uric acid (>425.5 µmol/L) were linked with poorer clinical outcome compared to patients with uric acid <425.5 µmol/L(P=0.027). Conclusion: Our findings suggests that uric acid is associated with the severity of PH and higher uric acid level serves as an important predictor for poor clinical outcome of PH patients.
Subject(s)
Cardiac Catheterization , Hypertension, Pulmonary/blood , Uric Acid/blood , Adult , Female , Humans , Male , Middle Aged , Prognosis , ROC Curve , Sensitivity and Specificity , Severity of Illness Index , Vascular ResistanceABSTRACT
Neuropathic pain occurs due to deleterious changes in the nervous system caused by a lesion or dysfunction. Currently, neuropathic pain management is unsatisfactory and remains a challenge in clinical practice. Studies have suggested that actin cytoskeleton remodeling may be associated with neural plasticity and may involve a nociceptive mechanism. Here, we found that the RhoA/LIM kinase (LIMK)/cofilin pathway, which regulates actin dynamics, was activated after chronic constriction injury (CCI) of the sciatic nerve. Treatments that reduced RhoA/LIMK/cofilin pathway activity, including simvastatin, the Rho kinase inhibitor Y-27632, and the synthetic peptide Tat-S3, attenuated actin filament disruption in the dorsal root ganglion and CCI-induced neuropathic pain. Over-activation of the cytoskeleton caused by RhoA/LIMK/cofilin pathway activation may produce a scaffold for the trafficking of nociceptive signaling factors, leading to chronic neuropathic pain. Here, we found that simvastatin significantly decreased the ratio of membrane/cytosolic RhoA, which was significantly increased after CCI, by inhibiting the RhoA/LIMK/cofilin pathway. This effect was highly dependent on the function of the cytoskeleton as a scaffold for signal trafficking. We conclude that simvastatin attenuated neuropathic pain in rats subjected to CCI by inhibiting actin-mediated intracellular trafficking to suppress RhoA/LIMK/cofilin pathway activity.
Subject(s)
Cofilin 1/metabolism , Lim Kinases/metabolism , Neuralgia/drug therapy , Signal Transduction/drug effects , Simvastatin/pharmacology , rhoA GTP-Binding Protein/metabolism , Actin Cytoskeleton/metabolism , Amides/pharmacology , Animals , Cytoskeleton/metabolism , Male , Neuralgia/metabolism , Phosphorylation/drug effects , Pyridines/pharmacology , Rats, Sprague-DawleyABSTRACT
Thirty volunteers randomly received either mild or deep propofol sedation, to assess its effect on explicit and implicit memory. Blood oxygen level-dependent functional magnetic resonance during sedation examined brain activation by auditory word stimulus and a process dissociation procedure was performed 4 h after scanning. Explicit memory formation did not occur in either group. Implicit memories were formed during mild but not deep sedation (p = 0.04). Mild propofol sedation inhibited superior temporal gyrus activation (Z value 4.37, voxel 167). Deep propofol sedation inhibited superior temporal gyrus (Z value 4.25, voxel 351), middle temporal gyrus (Z value 4.39, voxel 351) and inferior parietal lobule (Z value 5.06, voxel 239) activation. Propofol only abolishes implicit memory during deep sedation. The superior temporal gyrus is associated with explicit memory processing, while the formation of both implicit and explicit memories is associated with superior and middle temporal gyri and inferior parietal lobule activation.
Subject(s)
Anesthetics, Intravenous/pharmacology , Brain Mapping/methods , Dissociative Disorders/chemically induced , Magnetic Resonance Imaging/methods , Memory/drug effects , Propofol/pharmacology , Acoustic Stimulation/methods , Adult , Brain/drug effects , China , Conscious Sedation/methods , Deep Sedation/methods , Dose-Response Relationship, Drug , Humans , Male , Reference ValuesSubject(s)
Hypertension, Pulmonary/therapy , Pregnancy Complications/therapy , Adult , Anesthesia, Obstetrical , Female , Humans , Male , PregnancyABSTRACT
Among six fractions, including total extract and fractions of hexane, ethyl acetate, butanol, water and boiling water extracted and separated from wild sarsaparilla rhizome, the hexane fraction (HRW) was the most effective in eliminating four different human cancer cell lines with cellular viability less than 6.8%. HRW exhibited the highest potency against human leukaemia cells with an IC50 (concentration that inhibited the growth rate of cells by 50%) of 3.3 +/- 0.3 microg mL(-1), which was 17.6-fold smaller than that against normal human umbilical vein endothelial cells (IC50, 58.0 +/- 1.5 microg mL(-1)). For its rich natural resources, simple extraction procedure and high yield (3.2%), HRW has the potential to be developed as a selective anti-cancer nutraceutical or pharmaceutical natural health product with low side effects and high economical return.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/toxicity , Aralia/toxicity , Phytotherapy , Plant Extracts/toxicity , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Cell Line, Tumor , Cell Survival/drug effects , Female , HT29 Cells , Humans , Inhibitory Concentration 50 , Leukemia, T-Cell/pathology , Plant Extracts/chemistry , Rhizome/chemistryABSTRACT
Acute mediastinitis is a serious medical condition with a mortality rate from 30 to 40% or even higher. Early diagnosis with prompt and aggressive treatment is essential to prevent its rapid progression. Severe odynophagia and respiratory distress with positive neck or chest findings should raise suspicion of mediastinitis. We report a rare case of acute mediastinitis secondary to the unexpected migration of an impacted fish bone from the esophagus.
Subject(s)
Esophagus , Fishes , Foreign-Body Migration/complications , Mediastinitis/etiology , Acute Disease , Animals , Bone and Bones , Humans , Male , Mediastinitis/diagnostic imaging , Middle Aged , Tomography, X-Ray ComputedABSTRACT
We reviewed 100 patients with Guillan-Barré syndrome (GBS) from 1994 to 2000 from northwestern China. We examined clinical and electro-diagnostics features and compared them to patients from Europe, North America and northern China. Results indicated that among 100 patients with GBS, the demyelinating pattern was present in 51 patients, the axonal pattern in 25 patients, and 8 patients were inexcitable, 12 patients equivocal and 4 patients normal. The electrophysiological and clinical features of various subtypes of GBS in northwestern China seemed to be different in some ways from those in western countries and in northern China. However, in northwestern China, the demyelinating pattern is the major electrophysiological subtype.
Subject(s)
Guillain-Barre Syndrome/physiopathology , Adolescent , Adult , Aged , Child , Child, Preschool , China , Electromyography , Europe , Female , Humans , Male , Middle Aged , Motor Neurons/physiology , Neural Conduction/physiology , North AmericaABSTRACT
Experiments were performed in mice to investigate whether cyclooxygenase-2 (COX-2) in epithelial cells near the tubulovascular contact point (macula densa and TAL cells) may regulate renin gene expression in juxtaglomerular granular cells. Renin activity, afferent arteriolar granularity, and renin mRNA were determined in wild-type mice and in COX-2-knockout mice on control and low-NaCl diets. Renin activity in microdissected glomeruli assessed as angiotensin I formation in the presence of excess substrate and afferent arteriolar granularity determined by direct visualization and immunostaining were significantly reduced in COX-2 -/- compared with wild-type animals. Similarly, renal cortical mRNA levels were lower in COX-2 -/- than in wild-type mice. Maintaining mice on a low-salt diet for 14 days induced an increase in renin mRNA, afferent arteriolar granularity, and renin activity in wild-type mice. In contrast, renin mRNA and renin granularity did not significantly increase in low-salt-treated COX-2 -/- mice, whereas the increase in juxtaglomerular renin enzyme activity was markedly attenuated, but not fully blocked. In additional experiments we found that COX-2 mRNA was increased in angiotensin type 1A receptor-knockout mice compared with wild-type mice. We conclude that COX-2 in the tubulovascular contact region is a critical determinant of renin synthesis in granular cells under resting conditions and that it participates in the stimulation of renin expression caused by a low-NaCl intake.
Subject(s)
Diet, Sodium-Restricted , Isoenzymes/genetics , Prostaglandin-Endoperoxide Synthases/genetics , Renin/biosynthesis , Animals , Arterioles/cytology , Arterioles/metabolism , Cyclooxygenase 2 , Epithelial Cells/metabolism , Female , Glomerular Filtration Rate , Isoenzymes/deficiency , Juxtaglomerular Apparatus/blood supply , Juxtaglomerular Apparatus/cytology , Juxtaglomerular Apparatus/metabolism , Kidney Cortex/blood supply , Kidney Cortex/metabolism , Kidney Tubules/blood supply , Kidney Tubules/cytology , Kidney Tubules/metabolism , Mice , Mice, Knockout , Prostaglandin-Endoperoxide Synthases/deficiency , RNA, Messenger/biosynthesis , Receptor, Angiotensin, Type 1 , Receptors, Angiotensin/deficiency , Receptors, Angiotensin/genetics , Renin/geneticsABSTRACT
Induction of the inducible cyclooxygenase isoform COX-2 is likely to be an important mechanism for increased prostaglandin production in renal inflammation. We examined the effect of lipopolysaccharide (LPS) on regional renal COX-2 expression in the rat. In the inner medulla, LPS injection (4 mg/kg ip) induced a twofold and 2.5-fold increase in the levels of COX-2 mRNA and COX-2 protein, respectively. In contrast, COX-2 expression in the renal cortex was not significantly altered. COX-2 promoter transgenic mice were created using the 2.7-kb flanking region of the rat COX-2 gene. In these animals, LPS injection induced reporter gene expression predominately in the inner medulla. The LPS receptor CD14, usually regarded as a monocyte/macrophage-specific marker, was found to be abundantly expressed in the inner medulla and in dissected inner medullary collecting duct (IMCD) cells, suggesting that it may mediate medullary COX-2 induction. CD14 was present only at low levels in cortex and cortical segments, including glomeruli. In cultured cells, it was abundant in mouse IMCD (mIMCD-K2) cells and renal medullary interstitial cells, but largely undetectable in mesangial cells and M1 cells, a cell line derived from mouse cortical collecting ducts. In the mIMCD-K2 cell line, LPS significantly induced COX-2 mRNA expression, with concomitant induction of CD14. LPS-stimulated COX-2 expression was reduced by the addition of an anti-CD14 monoclonal antibody to the culture medium. These results demonstrate that LPS selectively stimulates COX-2 expression in the renal inner medulla through a CD14-dependent mechanism.
Subject(s)
Isoenzymes/biosynthesis , Kidney/metabolism , Lipopolysaccharide Receptors/physiology , Lipopolysaccharides/pharmacology , Prostaglandin-Endoperoxide Synthases/biosynthesis , Animals , Cyclooxygenase 2 , Isoenzymes/genetics , Kidney/cytology , Kidney/drug effects , Lipopolysaccharide Receptors/genetics , Male , Prostaglandin-Endoperoxide Synthases/genetics , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-DawleyABSTRACT
To determine the renal localization of oligopeptide transporters, Northern blot analyses were performed and polyclonal antisera were generated against PEPT1 and PEPT2, the two cloned rat H+/peptide transporters. Under high-stringency conditions, a 3.0-kb mRNA transcript of rat PEPT1 was expressed primarily in superficial cortex, whereas a 3.5-kb mRNA transcript of PEPT2 was expressed primarily in deep cortex/outer stripe of outer medulla. PEPT1 antisera detected a specific band on immunoblots of renal and intestinal brush-border membrane vesicles (BBMV) with an apparent mobility of approximately 90 kDa. PEPT2 antisera detected a specific broad band of approximately 85 kDa in renal but not in intestinal BBMV. PEPT1 immunolocalization experiments showed detection of a brush border antigen in S1 segments of the proximal tubule and in the brush border of villi from all segments of the small intestine. In contrast, PEPT2 immunolocalization was primarily confined to the brush border of S3 segments of the proximal tubule. All other nephron segments in rat were negative for PEPT1 and PEPT2 staining. Overall, our results conclusively demonstrate that although PEPT1 is expressed in early regions of the proximal tubule (pars convoluta), PEPT2 is specific for the latter regions of proximal tubule (pars recta).
Subject(s)
Carrier Proteins/analysis , Carrier Proteins/genetics , Kidney Tubules, Proximal/chemistry , Symporters , Animals , Antibody Specificity , Blotting, Northern , Carrier Proteins/immunology , Cloning, Molecular , DNA, Complementary , Fluorescent Antibody Technique , Gene Expression/physiology , Kidney Tubules, Proximal/metabolism , Male , Oligopeptides/metabolism , Peptide Transporter 1 , Protons , RNA, Messenger/analysis , Rats , Rats, Sprague-DawleyABSTRACT
In these experiments, we used a strain of angiotensin converting enzyme (ACE) germline null mutant mice, generated by J. H. Krege and co-workers (J. H. Krege, S. W. M. John, L. L. Langenbach, J. B. Hodgin, J. R. Hagaman, E. S. Bachman, J. C. Jennette, D. A. O'Brien, and O. Smithies. Nature 375: 146-148, 1995), to examine the effect of chronic ACE deficiency on the magnitude of tubuloglomerular feedback (TGF) responses. The genotype was determined by PCR on DNA extracted from the tail and was verified after each experiment by assessment of the blood pressure response to an injection of ANG I. To assess TGF responsiveness, we determined the change in stop-flow pressure (PSF) caused by increasing NaCl concentration at the macula densa by using micropuncture techniques. When loop of Henle flow rate was increased from 0 to 40 nl/min, PSF fell from a mean of 42.3 +/- 1.95 to 33.6 +/- 2.09 mmHg (n = 6, P = 0.005) in wild-type mice (+/+), fell from 40.6 +/- 2.35 to 38.6 +/- 1.93 mmHg in heterozygous (+/-) mice (n = 7, P = 0.014), and did not change in homozygous ACE (-/-) mice [36.7 +/- 2.02 mmHg vs. 36.4 +/- 2.01 mmHg; n = 4, P = not significant (NS)]. During an infusion of ANG II at a dose that did not significantly elevate blood pressure (70 ng. kg-1. min-1), TGF response magnitude (PSF 0 - PSF 40) increased from 6.5 +/- 1.4 to 9.8 +/- 1.19 mmHg in +/+ (P = 0.006), from 1.14 +/- 0.42 to 4.6 +/- 1.3 mmHg in +/- (P = 0.016), and from 0.42 +/- 0.25 to 4.02 +/- 1.06 in -/- mice (P = 0.05). Absence of TGF responses in ACE null mutant mice and restoration of near-normal responses during an acute infusion of ANG II supports previous conclusions that ANG II is an essential component in the signal transmission pathway that links the macula densa with the glomerular vascular pole.
Subject(s)
Feedback/physiology , Juxtaglomerular Apparatus/physiology , Kidney Glomerulus/metabolism , Kidney Tubules/metabolism , Peptidyl-Dipeptidase A/genetics , Angiotensin II/pharmacology , Animals , Blood Pressure/physiology , DNA Primers , Feedback/drug effects , Female , Genotype , Male , Mice , Mice, Knockout , Renal Circulation/drug effects , Renal Circulation/physiology , Renin-Angiotensin System/physiology , Sodium Chloride/pharmacology , Vasoconstriction/physiologyABSTRACT
The effect of the adenosine type 1 receptor agonist N6-cyclohexyladenosine (CHA) on glomerular vascular reactivity was studied in male angiotensin II type 1A (AT1A) receptor knockout mice (9). Vascular reactivity was assessed as the response of stop-flow pressure (PSF) to infusion of CHA into loops of Henle using micropuncture techniques. In AT1A +/+ mice at ambient arterial blood pressure (96.7 +/- 2.8 mmHg), the presence of CHA (10 (-5) M) in the perfusate increased PSF responses from 6.8 +/- 0.6 to 14.3 +/- 0.9 mmHg when the loop of Henle of the index nephron was perfused and from 0.7 +/- 0.3 to 12.3 +/- 1.0 mmHg when the loop of an adjacent nephron was perfused. At reduced arterial blood pressure (82.8 +/- 1. 3 mmHg), index nephron perfusion with CHA increased PSF responses from 4.5 +/- 0.3 to 9.4 +/- 0.4 mmHg. In AT1A -/- mice with a mean arterial blood pressure of 80 +/- 1.9 mmHg, CHA increased PSF responses only from 0.1 +/- 0.3 to 3.6 +/- 0.54 mmHg during index nephron perfusion and from 0.25 +/- 0.2 to 2.7 +/- 0.55 mmHg during adjacent nephron perfusion, significantly less than in wild-type animals (P < 0.001). Responses to CHA were intermediate in AT1A +/- mice. Thus AT1A receptor knockout mice show a markedly reduced constrictor response to CHA both in the presence and absence of simultaneous activation of the tubuloglomerular feedback system. These data support the notion of a functional interaction between adenosine and angiotensin II in the regulation of afferent arteriolar tone.
Subject(s)
Kidney Glomerulus/blood supply , Receptors, Angiotensin/deficiency , Receptors, Purinergic P1/physiology , Renal Circulation/physiology , Vasoconstriction/physiology , Adenosine/analogs & derivatives , Adenosine/pharmacology , Animals , Blood Pressure/physiology , Male , Mice , Mice, Knockout/genetics , Perfusion , Pressure , RNA, Messenger/metabolism , Receptors, Angiotensin/genetics , Receptors, Purinergic P1/genetics , Vasomotor System/drug effectsABSTRACT
Luminal [NaCl] at the macula densa (MD) has two established effects: regulation of glomerular arteriolar resistance through tubuloglomerular feedback (TGF) and control of renin secretion. TGF acts as a minute-to-minute stabilizer of distal salt delivery, thereby minimizing the impact of random perturbations in filtration and absorption forces on NaCl excretion. During long-lasting perturbations of MD [NaCl], control of renin secretion becomes the dominant function of the MD. The potentially maladaptive effect of TGF under chronic conditions is prevented by TGF adaptations permitting adjustments in glomerular filtration rate to occur. TGF adaptation is mechanistically coupled to the endpoint targeted by chronic deviations in MD [NaCl], the rate of local and systemic angiotensin II generation. Studies of TGF in transgenic mice are expected to provide further insights into the mechanisms mediating between luminal [NaCl] and afferent arterioles. TGF responses are virtually abolished in mice in which either the AT1A gene or the angiotensin converting enzyme gene is rendered nonfunctional by homologous recombination. In contrast, TGF responses are unaltered in nitric oxide synthase I knockout mice. Thus, an intact renin-angiotensin system appears to be critical for the TGF signaling pathway.