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

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