Purpose <p>To elucidate whether systemic blood pressure affects retinal ganglion cell (RGC) survival in rats administered systemic aldosterone</p> Study design <p>Experimental study design</p> Methods <p>Rats were continuously administered aldosterone or vehicle via a subcutaneous osmotic mini-pump. Hypertension was induced by the provision of saline as their drinking water. Systolic and diastolic blood pressures and intraocular pressure (IOP) were measured at the baseline and at 1–6&#xa0;weeks after administration of aldosterone-water, aldosterone-saline, vehicle-water, or vehicle-saline. The number of retrogradely labelled RGCs in retinal flat mounts were counted after 6 weeks of treatment. Aldosterone-treated rats also received eplerenone (a mineralocorticoid receptor antagonist) or hydralazine (a vasodilator), and changes in systolic and diastolic blood pressures, IOP, and the number of RGCs were examined.</p> Results <p>The number of RGCs was significantly reduced in rats treated with aldosterone, regardless of whether they drank water or saline (aldosterone/saline group vs vehicle/saline group: 1464.8 ± 29.7 vs 1763.3 ± 106.5, respectively, <i>P</i> = 0.01; aldosterone/water group vs vehicle/water group: 1433.3 ± 30.2 vs 1815.0 ± 193.9, respectively, <i>P</i> &lt;0.01). No change in IOP with aldosterone or saline administration was observed (<i>P</i> &gt;0.05). Although eplerenone or hydralazine treatment in animals receiving aldosterone and saline reduced the systolic and diastolic blood pressures as compared with in the controls, the number of RGCs was only preserved in the eplerenone-treated group (eplerenone group vs control group: 1868.5 ± 177.7 vs 1464.8 ± 29.7, respectively, <i>P</i> &lt;0.01; hydralazine group vs control group 1554.5 ± 34.9 vs 1464.8 ± 29.7, respectively, <i>P</i> = 0.48). No change in IOP after eplerenone or hydralazine treatment was observed (<i>P</i> &gt;0.05).</p> Conclusion <p>Aldosterone-induced RGC loss is not affected by systemic blood pressure or IOP.</p>