Proceedings of The Physiological Society

University College Cork (2004) J Physiol 560P, C3

Communications

ROLE OF OXIDATIVE STRESS ON THE RENAL MICROVASCULATURE OF ANAESTHETISED WISTAR AND STROKE PRONE SPONTANEOUSLY HYPERTENSIVE RATS (SHRSP)

Ahmeda,Ahmad F; Johns,Edward J;

1. Department of Physiology, University College Cork, Cork, Ireland.


A range of autocrine and paracrine factors influence basal tone of the renal microvasculature. Important amongst these are the reactive oxygen species (ROS) and include super oxide anions, hydrogen peroxide (H2O2) and nitric oxide (NO), which are generated to differing degrees in various situations. This study aimed to investigate the impact of ROS on perfusion of blood through the renal cortex and medulla normally and in a hypertensive state. Eight groups (n= 6-7) of male Wistar and SHRSP, 250-300g, were anaesthetised with an I.P injection of 1 ml chloralose/urethane, 16.5/250 mg/ml. The right femoral vein was cannulated for infusion of saline (154mM NaCl) at 3ml/h and supplemental doses of anaesthetic. The right femoral artery was cannulated for measurement of blood pressure (BP). The left kidney was exposed via a flank incision, placed in a holder and a small cannula was inserted 4.5mm into the kidney for intramedullary (i-m) infusion of saline or drugs at 0.6-1.0 ml/h. Two Laser-Doppler microprobes (each 0.5 mm diameter) were inserted 1.5 and 4.0 mm into the kidney to measure cortical and medullary blood perfusion, respectively (100 perfusion units (PU) = 1 V). After 90min, baseline measurements were taken, then either vehicle, tempol, a super oxide dismutase (SOD) mimetic, 30 μmol/kg/min, diethyl-dithio-carbamate (DETC), a SOD inhibitor, 2 mg/kg/min, or a combination of tempol 30μmol/kg/min plus Catalase (an enzyme degrading H2O2) 5000 I.U were infused i-m for 60 min. At the end of the experiments the animals were killed with an anaesthetic overdose. Data ± SEM were subjected to the Student′s t-test and significance taken at P<0.05. In the Wistar rats, baseline levels of BP were 101±15 mmHg, for cortical perfusion (CP), 210±24 PU and medullary perfusion (MP) 119±15 PU and for the SHRSP, BP was 131±9 mmHg, CP was 269±48 PU, and MP was 90±20 PU. Administration of tempol had no effect on CP in either Wistar or SHRSP but increased MP in the Wistar rats by 13±5% (P<0.05) and in the SHRSP by 26±10% (P<0.05). Intramedullary DETC decreased CP and MP 10±2% and 13±3%, respectively (P<0.05) in the Wistar rats while in the SHRSP CP fell by 11±3% (P<0.05) and MP by 21±4%. Catalase + Tempol infused i-m, increased CP in both Wistar and SHRSP, by 16±7% and 18±9%, respectively, and MP rose to a greater degree, by 39±6% and 50±9% respectively (both P<0.05), in the Wistar and SHRSP, respectively. These results indicate that ROS can determine the level of tone in the renal microvasculature to a greater extent in the medulla than cortex. Moreover, the impact of ROS in the renal medulla of the SHRSP is relatively greater, suggesting a raised degree of oxidative stress.

Where applicable, experiments conform with Society ethical requirements