The role of angiotensin in etiology of cardiovascular diseases especially in hypertension is well established. Renin-angiotensin-aldosterone contributes to the development and maintenance of hypertension directly by increases in vascular tone and renal sodium reabsorption or indirectly by increasing oxidative stress and inflammation. Contrary to this pathological arm, angiotensin (Ang) 1-7 via Mas receptors has been reported to protect the cardiovascular function although the exact mechanism is not yet clear. We have previously shown that oxidative stress leads to renal dopamine D1 receptor (D1R) dysfunction which could disrupt sodium regulation and subsequently lead to hypertension. In here we wanted to test whether chronic administration of Ang 1-7 in mice could mitigate oxidative stress, protect renal D1R function and prevent development of hypertension. Mice (C57BL) were implanted with telemetry probes and concomitantly treated with L-buthionine sulfoximine (BSO, in drinking water) and Ang 1-7 (via jugular vein by osmotic pumps). Control (C, no treatment) and shams (implanted with saline filled pumps) exhibited similar behavioral and physiological parameters. Mice treated with BSO alone exhibited increased oxidative stress and high BP as compared to controls. Ang 1-7 treatment did not affect oxidative stress and BP in control mice but prevented the increase in BP and oxidative milieu in BSO treated mice. Mean arterial pressure (mmHg), C: 78.5 ± 2.3*; BSO: 97.3 ± 3.8; Ang 1-7: 80.1* ± 4.1; BSO+Ang 1-7: 83.2 ± 3.4*, *P <0.05 vs BSO. SKF38393, a D1R agonist, increased urine and sodium excretion in control mice but failed to induce diuresis or natriuresis in BSO-treated mice. Treatment with Ang 1-7 protected D1R function as both natriuresis and diuresis was observed in mice treated with BSO plus Ang 1-7. Chronic Ang 1-7 had no effect on D1R function in the absence of BSO. These data show that oxidative stress leads to hypertension by disrupting renal D1R dependent sodium regulation. Ang 1-7 mitigates oxidative stress, protects renal D1R function and prevents increase in BP. This study provides a new insight on how beneficial arm of Ang system could protect renal D1R-mediated sodium regulation and prevent development of hypertension during oxidative stress.
Transcription Factor Nrf2 Protects Renal Dopamine D1 Receptor Function During Oxidative Stress