P47 Hydrogen Sulfide reduces hypertension, proteinuria and renal damage

Abstract

Background Hypertension and proteinuria are important mediators of renal damage. Despite therapeutic intervention, many renal patients ultimately progress to end stage renal disease. Hydrogen sulfide (H 2 S) is, in addition to nitric oxide and carbon monoxide, acknowledged as the third gasotransmitter sharing many physiological functions with these gases. It has vasodilatory, anti-inflammatory and anti-oxidant properties, making it an attractive candidate for pharmacological use in renal disease. We therefore investigated the protective properties of the H 2 S donor sodium hydrosulfide (NaHS) in Angiotensin II (AngII)-induced renal disease in rats. Methods Male Sprague Dawley rats were infused with AngII (435 ng/kg/min) or saline (control) for three weeks via subcutaneously placed osmotic minipumps. At placement of the pumps, rats were randomized to two different treatment regimens (vehicle and NaHS 5.6 mg/kg/day) and treated with intra-peritoneal injections twice a day during the three weeks of AngII infusion (n = 7/group). Control animals (n = 6) received vehicle injections only. Twenty-four hour urine was collected weekly. After three weeks, intra-aortic blood pressure was measured under anesthesia and subsequently rats were sacrificed. Upon sacrifice, plasma and kidneys were collected. Renal tissue was studied for tubular epithelial damage (Kidney Injury Molecule-1 (KIM-1)), interstitial fibrosis (collagen III), and upregulation of NADPH oxidase (NOX2). In an ex vivo experiment, rat kidneys (n = 4) in an isolated perfused kidney (IPK) setup were pre-contracted with phenylephrine (PE) (1uM) and subjected to 1 mM NaHS for 1 min. Before and after NaHS treatment intra-renal pressure was measured. Results Compared to controls, AngII infusion caused a 48% increase of systolic blood pressure (SBP) (142 vs 212 mmHg, p vs 346 mg/24 h, p vs 1.4 ml/min, p vs 212 mmHg, p vs 346 mg/24 h, p vs 1.4 ml/min, p Conclusion AngII induced hypertension, proteinuria and subsequent renal damage are markedly decreased by treatment with NaHS. Blood pressure regulation is a possible mechanism of renal tissue protection, but anti-proteinuric, anti-inflammatory and anti-oxidant effects may also play a role. Our data show that H 2 S might be a valuable addition to the already existing anti-hypertensive and reno-protective therapies.