Abstract
Previous studies have demonstrated that intramedullary inhibition of heme oxygenase‐1 (HO‐1) increases the blood pressure response to angiotensin II (Ang II) infusion. The increase in blood pressure was associated with an increase in renal medullary superoxide production. The current study was designed to test the hypothesis that increased renal medullary superoxode production contributes to the increase in blood pressure in response to blockade of renal medullary HO‐1 in Ang II hypertension. Male C57BL/6J mice (16–20 weeks of age) were implanted with chronic intrarenal medullary interstitial (IRMI) and infused with: saline, Tempol (T; 6mM), the HO‐1 inhibitor QC‐13 (25 μM), or a combination of T + QC‐13. T treatment was started 2 days before infusion of QC‐13 and IRMI infusions were switched 4 days prior to implantation of Ang II containing osmotic minipumps which infused Ang II at a rate of 1 μg/kg/min. Blood pressures on days 7–10 post Ang II infusion averaged 150 ± 3 mmHg in mice receiving IRMI infusion of saline. IRMI infusion of T alone decreased blood pressure to 136 ± 3 mmHg. IRMI infusion of QC‐13 alone increased blood pressure to 164 ± 2 (p<0.05) and IRMI infusion of T along with QC‐13 significantly attenuated the rise in blood pressure to 142 ± 2 mmHg (p<0.05). These results demonstrated that blockade of intrarenal medullary superoxide production with T attenuates the increase in blood pressure in response to intrarenal medullary inhibition of HO‐1. These results support the important role for the antioxidant actions of HO‐1 metabolites in the renal medulla in the regulation of blood pressure.
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