Angiotensin II Type 1 Receptors and Systemic Hemodynamic and Renal Responses to Stress and Altered Blood Volume in Conscious Rabbits

We examined how systemic blockade of type 1 angiotensin (AT1-) receptors affects reflex control of the circulation and the kidney. In conscious rabbits, the effects of candesartan on responses of systemic and renal hemodynamics and renal excretory function to acute hypoxia, mild hemorrhage, and plasma volume expansion were tested. Candesartan reduced resting mean arterial pressure (MAP, −8 ± 2%) without significantly altering cardiac output (CO), increased renal blood flow (RBF, +38 ± 9%) and reduced renal vascular resistance (RVR, −32 ± 6%). Glomerular filtration rate (GFR) was not significantly altered but sodium excretion (UNa+V) increased fourfold. After vehicle treatment, hypoxia (10% inspired O2 for 30 min) did not significantly alter MAP or CO, but reduced heart rate (HR, −17 ± 6%), increased RVR (+33 ± 16%) and reduced GFR (−46 ± 16%) and UNa+V (−41 ± 17%). Candesartan did not significantly alter these responses. After vehicle treatment, plasma volume expansion increased CO (+35 ± 7%), reduced total peripheral resistance (TPR, −26 ± 5%), increased RBF (+62 ± 23%) and reduced RVR (−32 ± 9%), but did not significantly alter MAP or HR. It also increased UNa+V (803 ± 184%) yet reduced GFR (−47 ± 9%). Candesartan did not significantly alter these responses. After vehicle treatment, mild hemorrhage did not significantly alter MAP but increased HR (+16 ± 3%), reduced CO (−16 ± 4%) and RBF (−18 ± 6%), increased TPR (+18 ± 4%) and tended to increase RVR (+18 ± 9%, P = 0.1), but had little effect on GFR or UNa+V. But after candesartan treatment MAP fell during hemorrhage (−19 ± 1%), while neither TPR nor RVR increased, and GFR (−64 ± 18%) and UNa+V (−83 ± 10%) fell. AT1-receptor activation supports MAP and GFR during hypovolemia. But AT1-receptors appear to play little role in the renal vasoconstriction, hypofiltration, and antinatriuresis accompanying hypoxia, or the systemic and renal vasodilatation and natriuresis accompanying plasma volume expansion

Disruption of transitional stages in 24-h blood pressure recording in renal transplant recipients

Patients with kidney replacement exhibit disrupted circadian rhythms. Most studies measuring blood pressure use the dipper/non-dipper classification, which does not consider analysis of transitional stages between low and high blood pressure, confidence intervals nor shifts in the time of peak, while assuming subjective onsets of night and day phases. In order to better understand the nature of daily variation of blood pressure in these patients, we analyzed 24 h recordings from 41 renal transplant recipients using the non-symmetrical double-logistic fitting assessment which does not assume abruptness nor symmetry in ascending and descending stages of the blood pressure profile, and a cosine best-fitting regression method (Cosinor). Compared with matched controls, double-logistic fitting showed that the times for most transitional stages (ascending systolic and descending systolic, diastolic, and mean arterial pressure) had a wider distribution along the 24-h. The proportion of individuals without daily blood pressure rhythm in the transplanted group was larger only for systolic arterial pressure, and the amplitude showed no significant difference. Furthermore, the transplant recipient group had a less pronounced slope in descending systolic and ascending mean blood pressure. Cosinor analysis confirmed this phase-related changes, showing a wider distribution of times of peak (acrophases). We conclude that daily disruptions in renal transplant recipients can be explained not necessarily by an absence in diurnal variation, but also by changes in waveform-related parameters of the rhythm, and that alterations in the phase of the rhythm are the most consistent finding in these patients.Fil: Katz, Marcelo E.. Universidad Nacional de Quilmes; ArgentinaFil: Margulis, Fernando. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; ArgentinaFil: Schiavelli, Rubén. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; ArgentinaFil: Arias, Pablo. Universidad de Buenos Aires; ArgentinaFil: Head, Geoffrey A.. No especifíca;Fil: Golombek, Diego Andres. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Ossification of the Posterior Longitudinal Ligament: Surgical Approaches and Associated Complications.

Ossification of the posterior longitudinal ligament (OPLL) is a rare but potentially devastating cause of degenerative cervical myelopathy (DCM). Decompressive surgery is the standard of care for OPLL and can be achieved through anterior, posterior, or combined approaches to the cervical spine. Surgical correction of OPLL via any approach is associated with higher rates of complications and the presence of OPLL is considered a significant risk factor for perioperative complications in DCM surgeries. Potential complications include dural tear (DT) and subsequent cerebrospinal fluid leak, C5 palsy, hematoma, hardware failure, surgical site infections, and other neurological deficits. Anterior approaches are technically more demanding and associated with higher rates of DT but offer greater access to ventral OPLL pathology. Posterior approaches are associated with lower rates of complications but may allow for continued disease progression. Therefore, the decision to pursue either an anterior or posterior approach to surgical decompression may be critically influenced by complications associated with each procedure. The authors critically review anterior and posterior approaches to surgical decompression of OPLL with particular focus on the complications associated with each approach. We also review the recent work in developing new surgical treatments for OPLL that aim to reduce complication incidence

Short term fat feeding rapidly increases plasma insulin but does not result in dyslipidaemia

Although the association between obesity and hypertension is well known, the underlying mechanism remains elusive. Previously, we have shown that 3 week fat feeding in rabbits produces greater visceral adiposity, hypertension, tachycardia and elevated renal sympathetic nerve activity compared to rabbits on a normal diet. Because hyperinsulinaemia, hyperleptinemia and dyslipidaemia are independent cardiovascular risk factors associated with hypertension we compared plasma insulin, leptin and lipid profiles in male New Zealand White rabbits fed a normal fat diet (NFD 4.3% fat, n = 11) or high fat diet (HFD 13.4% fat, n = 13) at days 1, 2, 3 and weeks 1, 2, 3 of the diet. Plasma concentrations of diacylglyceride (DG), triacylglyceride (TG), ceramide and cholesteryl esters (CE) were obtained after analysis by liquid chromatography mass spectrometry. Plasma insulin and glucose increased within the first 3 days of the diet in HFD rabbits (P 0.05), increasing by week 3 in fat fed animals alone (P 0.05). Our data show plasma insulin increases rapidly following consumption of a HFD and suggests that it may play a role in the rapid rise of blood pressure. Dyslipidaemia does not appear to contribute to the hypertension in this animal model

Material Units, Structures/Landforms, and Stratigraphy for the Global Geologic Map of Ganymede (1:15M)

In the coming year a global geological map of Ganymede will be completed that represents the most recent understanding of the satellite on the basis of Galileo mission results. This contribution builds on important previous accomplishments in the study of Ganymede utilizing Voyager data and incorporates the many new discoveries that were brought about by examination of Galileo data. Material units have been defined, structural landforms have been identified, and an approximate stratigraphy has been determined utilizing a global mosaic of the surface with a nominal resolution of 1 km/pixel assembled by the USGS. This mosaic incorporates the best available Voyager and Galileo regional coverage and high resolution imagery (100-200 m/pixel) of characteristic features and terrain types obtained by the Galileo spacecraft. This map has given us a more complete understanding of: 1) the major geological processes operating on Ganymede, 2) the characteristics of the geological units making up its surface, 3) the stratigraphic relationships of geological units and structures, and 4) the geological history inferred from these relationships. A summary of these efforts is provided here

Deficiency of MicroRNA-181a results in transcriptome-wide cell-specific changes in the kidney and increases blood pressure

MicroRNA miR-181a is downregulated in the kidneys of hypertensive patients and hypertensive mice. In vitro, miR-181a is a posttranslational inhibitor of renin expression, but pleiotropic mechanisms by which miR-181a may influence blood pressure (BP) are unknown. Here, we determined whether deletion of miR-181a/b-1 in vivo changes BP and the molecular mechanisms involved at the single-cell level. We developed a KO (knockout) mouse model lacking miR-181a/b-1 genes using CRISPR/Cas9 technology. Radiotelemetry probes were implanted in 12-week-old C57BL/6J WT (wild type) and miR-181a/b-1 KO mice. Systolic and diastolic BP were 4- to 5-mm Hg higher in KO compared with WT mice over 24 hours (P<0.01). Compared with WT mice, renal renin was higher in the juxtaglomerular cells of KO mice. BP was similar in WT mice on a high- (3.1%) versus low- (0.3%) sodium diet (+0.4 +/- 0.8 mm Hg), but KO mice showed salt sensitivity (+3.3 +/- 0.8 mm Hg; P<0.001). Since microRNAs can target several mRNAs simultaneously, we performed single-nuclei RNA sequencing in 6699 renal cells. We identified 12 distinct types of renal cells, all of which had genes that were dysregulated. This included genes involved in renal fibrosis and inflammation such as Stat4, Col4a1, Cd81, Flt3l, Cxcl16, and Smad4. We observed upregulation of pathways related to the immune system, inflammatory response, reactive oxygen species, and nerve development, consistent with higher tyrosine hydroxylase in the kidney. In conclusion, downregulation of the miR-181a gene led to increased BP and salt sensitivity in mice. This is likely due to an increase in renin expression in juxtaglomerular cells, as well as microRNA-driven pleiotropic effects impacting renal pathways associated with hypertension

Angiotensin type 1A receptors in C1 neurons of the rostral ventrolateral medulla modulate the pressor response to aversive stress

The rise in blood pressure during an acute aversive stress has been suggested to involve activation of angiotensin type 1A receptors (AT(1A)Rs) at various sites within the brain, including the rostral ventrolateral medulla. In this study we examine the involvement of AT(1A)Rs associated with a subclass of sympathetic premotor neurons of the rostral ventrolateral medulla, the C1 neurons. The distribution of putative AT(1A)R-expressing cells was mapped throughout the brains of three transgenic mice with a bacterial artificial chromosome-expressing green fluorescent protein under the control of the AT(1A)R promoter. The overall distribution correlated with that of the AT(1A)Rs mapped by other methods and demonstrated that the majority of C1 neurons express the AT(1A)R. Cre-recombinase expression in C1 neurons of AT(1A)R-floxed mice enabled demonstration that the pressor response to microinjection of angiotensin II into the rostral ventrolateral medulla is dependent upon expression of the AT(1A)R in these neurons. Lentiviral-induced expression of wild-type AT(1A)Rs in C1 neurons of global AT(1A)R knock-out mice, implanted with radiotelemeter devices for recording blood pressure, modulated the pressor response to aversive stress. During prolonged cage-switch stress, expression of AT(1A)Rs in C1 neurons induced a greater sustained pressor response when compared to the control viral-injected group (22 +/- 4 mmHg for AT(1A)R vs 10 +/- 1 mmHg for GFP; p < 0.001), which was restored toward that of the wild-type group (28 +/- 2 mmHg). This study demonstrates that AT(1A)R expression by C1 neurons is essential for the pressor response to angiotensin II and that this pathway plays an important role in the pressor response to aversive stress

The Implications of Paraspinal Muscle Atrophy in Low Back Pain, Thoracolumbar Pathology, and Clinical Outcomes After Spine Surgery: A Review of the Literature.

STUDY DESIGN: Literature review. OBJECTIVES: Paraspinal muscle integrity is believed to play a critical role in low back pain (LBP) and numerous spinal deformity diseases and other pain pathologies. The influence of paraspinal muscle atrophy (PMA) on the clinical and radiographic success of spinal surgery has not been established. We aim to survey the literature in order to evaluate the impact of paraspinal muscle atrophy on low back pain, spine pathologies, and postoperative outcomes of spinal surgery. METHODS: A review of the literature was conducted using a total of 267 articles identified from a search of the PubMed database and additional resources. A full-text review was conducted of 180 articles, which were assessed based on criteria that included an objective assessment of PMA in addition to measuring its relationship to LBP, thoracolumbar pathology, or surgical outcomes. RESULTS: A total of 34 studies were included in this review. The literature on PMA illustrates an association between LBP and both decreased cross-sectional area and increased fatty infiltration of paraspinal musculature. Atrophy of the erector spinae and psoas muscles have been associated with spinal stenosis, isthmic spondylolisthesis, facet arthropathy, degenerative lumbar kyphosis. A number of studies have also demonstrated an association between PMA and worse postoperative outcomes. CONCLUSIONS: PMA is linked to several spinal pathologies and some studies demonstrate an association with worse postoperative outcomes following spinal surgery. There is a need for further research to establish a relationship between preoperative paraspinal muscle integrity and postoperative success, with the potential for guiding surgical decision making