Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary. We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats. This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation. Exogenous angiotensin-II reduced renal cortical tissue PO2 more than equi-pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine. Activation of the endogenous renin-angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin-II receptor type 1 antagonist. Angiotensin-II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. We hypothesised that both exogenous and endogenous angiotensin-II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose-dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi-pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min(-1) . Equi-pressor infusion of phenylephrine did not significantly reduce RBF or renal oxygen delivery. Activation of the endogenous renin-angiotensin system in Cyp1a1Ren2 transgenic rats reduced cortical tissue PO2. This could be reversed within minutes by pharmacological angiotensin-II receptor type 1 (AT1 R) blockade. Thus AngII is an important modulator of renal cortical oxygenation via AT1 receptors. AngII had a greater influence on cortical oxygenation than did phenylephrine. This phenomenon appears to be attributable to the profound impact of AngII on renal oxygen delivery. We conclude that the ability of AngII to promote renal cortical hypoxia may contribute to its influence on initiation and progression of chronic kidney diseas

Management of initial orthostatic hypotension: lower body muscle tensing attenuates the transient arterial blood pressure decrease upon standing from squatting

A B S T R A C T IOH (initial orthostatic hypotension) comprises symptoms of cerebral hypoperfusion caused by an abnormally large transient MAP (mean arterial pressure) decrease 5-15 s after arising from a supine, sitting or squatting position. Few treatment options are available. In the present study, we set out to test the hypothesis that LBMT (lower body muscle tensing) attenuates IOH after rising from squatting and its symptoms in daily life. A total of 13 IOH patients (nine men; median age, 27 years) rose from squatting twice, once with LBMT and once without. In addition, seven healthy volunteers (five men; median age, 27 years) were studied in a cross-over study design. They stood up from the squatting position three times, once combined with LBMT. Blood pressure (Finometer) was measured continuously, and CO (cardiac output) by Modelflow and TPR (total peripheral resistance) were computed. MAP, CO and TPR were compared without and with LBMT. Using a questionnaire, the perceived effectiveness of LBMT in the patients' daily lives was evaluated. With LBMT, the minimal MAP after standing up was higher in both groups (19 mmHg in patients and 13 mmHg in healthy subjects). In healthy subjects, the underlying mechanism was a blunted TPR decrease (to 47 % compared with 60 %; P < 0.05), whereas in the patients no clear CO or TPR pattern was discernible. During follow-up, eight out of ten patients using LBMT reported fewer IOH symptoms. In conclusion, LBMT is a new intervention to attenuate the transient blood pressure decrease after standing up from squatting, and IOH patients should be advised about the use of this manoeuvre

Tumor Ulceration Does Not Fully Explain Sex Disparities in Melanoma Survival among Adolescents and Young Adults

Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from paediatric to adult care) influences control of hypertension. We assessed the prevalence of hypertension and uHT among Dutch paediatric and young adult KTRs and analysed the effects of transition. Additionally, we made an inventory of variations in treatment policies in Dutch transplant centres. Cross-sectional and longitudinal national data from living KTRs a parts per thousand currency sign30 years of age (a parts per thousand yen1-year post-transplant, eGFR > 20 mL/min) were extracted from the 'RICH Q' database, which comprises information about all Dutch KTRs <19 years of age, and the Netherlands Organ Transplant Registry database for adult KTRs (a parts per thousand yen18-30 years of age). We used both upper-limit blood pressure (BP) thresholds for treatment according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. uHT was defined as a BP above the threshold. A questionnaire on treatment policies was sent to paediatric and adult nephrologists at eight Dutch transplant centres. Hypertension and uHT were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Time after transplantation was comparable between these groups. Longitudinal analysis showed no evidence of effect of transition on systolic BP or prevalence of uHT. Policies vary considerably between and within centres on the definition of hypertension, BP measurement and antihypertensive treatment. Average BP in KTRs increases continuously with age between 6 and 30 years. Young adult KTRs have significantly more uHT than paediatric KTRs according to KDIGO guidelines. Transition does not influence the prevalence of uHT

Dissection of carotid sinus hypersensitivity: the timing of vagal and vasodepressor effects and the effect of body position

We assessed the timing of vagal and sympathetic factors that mediate hypotension during CSM (carotid sinus massage) in patients with carotid sinus hypersensitivity. We hypothesized that a fall in cardiac output would precede vasodepression, and that vasodepression would be exaggerated by head-up tilt. We performed pulse contour analyses on blood pressure recordings during CSM in syncope patients during supine rest and head-up tilt. In a subset we simultaneously recorded muscle sympathetic nerve activity supine. During supine rest, systolic blood pressure decreased from 150±7 to 107±7 mmHg (P <0.001) and heart rate from 64±2 to 39±3 beats/min (P <0.01). Cardiac output decreased with heart rate to nadir (66±6% of baseline), 3.1±0.4 s after onset of bradycardia. In contrast, total peripheral resistance reached nadir (77±3% of baseline) after 11±1 s. During head-up-tilt, systolic blood pressure fell from 149±10 to 90±11 mmHg and heart rate decreased from 73±4 to 60±7 beats/min. Compared with supine rest, cardiac output nadir was lower (60±8 compared with 83±4%, P <0.05), whereas total peripheral resistance nadir was similar (81±6 compared with 80±3%). The time to nadir from the onset of bradycardia did not differ from supine rest. At the onset of bradycardia there was an immediate withdrawal of muscle-sympathetic nerve activity while total peripheral resistance decay occurred much later (6-8 s). The haemodynamic changes following CSM have a distinct temporal pattern that is characterized by an initial fall in cardiac output (driven by heart rate), followed by a later fall in total peripheral resistance, even though sympathetic withdrawal is immediate. This pattern is independent of body positio

Hypoglycemia unawareness: meld het bij het CBR

The Dutch legislator has adopted the point of view that people with diabetes and hypoglycaemia unawareness are unfit for driving a motor vehicle because hypoglycaemia unawareness carries with it an unacceptable risk for traffic accidents. There is no legal obligation for people in possession of a driving license to report changes to their state of health such as the appearance of hypoglycaemia unawareness. We argue that patients with newly diagnosed diabetes should inform the Driving Test Organisation about changes to their health status for moral reasons, and for reasons of judicial liability. This subject should be included in patient education, as should be strategies to minimise the risk of hypoglycaemia. In exceptional cases, the physician may opt to breech medical confidentiality and report the presence of hypoglycaemia unawareness in order to avert immediate, severe dange

Management of initial orthostatic hypotension: lower body muscle tensing attenuates the transient arterial blood pressure decrease upon standing from squatting

IOH (initial orthostatic hypotension) comprises symptoms of cerebral hypoperfusion caused by an abnormally large transient MAP (mean arterial pressure) decrease 5-15 s after arising from a supine, sitting or squatting position. Few treatment options are available. In the present study, we set out to test the hypothesis that LBMT (lower body muscle tensing) attenuates IOH after rising from squatting and its symptoms in daily life. A total of 13 IOH patients (nine men; median age, 27 years) rose from squatting twice, once with LBMT and once without. In addition, seven healthy volunteers (five men; median age, 27 years) were studied in a cross-over study design. They stood up from the squatting position three times, once combined with LBMT. Blood pressure (Finometer) was measured continuously, and CO (cardiac output) by Modelflow and TPR (total peripheral resistance) were computed. MAP, CO and TPR were compared without and with LBMT Using a questionnaire, the perceived effectiveness of LBMT in the patients' daily lives was evaluated. With LBMT, the minimal MAP after standing up was higher in both groups (19 mmHg in patients and 13 mmHg in healthy subjects). In healthy subjects, the underlying mechanism was a blunted TPR decrease (to 47% compared with 60%; P <0.05), whereas in the patients no clear CO or TPR pattern was discernible. During follow-up, eight out of ten patients using LBMT reported fewer IOH symptoms. In conclusion, LBMT is a new intervention to attenuate the transient blood pressure decrease after standing up from squatting, and IOH patients should be advised about the use of this mancieuvr