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Renal tissue oxygen tension (PO2) and its determinants have not been quantified in polycystic kidney disease (PKD). Therefore, we measured kidney tissue PO2 in the Lewis rat model of PKD (LPK) and in Lewis control rats. We also determined the relative contributions of altered renal oxygen delivery and consumption to renal tissue hypoxia in LPK rats. PO2 of the superficial cortex of 11- to 13-wk-old LPK rats, measured by Clark electrode with the rat under anesthesia, was higher within the cysts (32.8 ± 4.0 mmHg) than the superficial cortical parenchyma (18.3 ± 3.5 mmHg). PO2 in the superficial cortical parenchyma of Lewis rats was 2.5-fold greater (46.0 ± 3.1 mmHg) than in LPK rats. At each depth below the cortical surface, tissue PO2 in LPK rats was approximately half that in Lewis rats. Renal blood flow was 60% less in LPK than in Lewis rats, and arterial hemoglobin concentration was 57% less, so renal oxygen delivery was 78% less. Renal venous PO2 was 38% less in LPK than Lewis rats. Sodium reabsorption was 98% less in LPK than Lewis rats, but renal oxygen consumption did not significantly differ between the two groups. Thus, in this model of PKD, kidney tissue is severely hypoxic, at least partly because of deficient renal oxygen delivery. Nevertheless, the observation of similar renal oxygen consumption, despite markedly less sodium reabsorption, in the kidneys of LPK compared with Lewis rats, indicates the presence of inappropriately high oxygen consumption in the polycystic kidney., (Copyright © 2014 the American Physiological Society.)

The complex role of the renin-angiotensin-system (RAS) in arterial pressure regulation has been well documented. Recently, we demonstrated that chronic low-dose angiotensin II (ANG II) infusion decreases arterial pressure in female rats via an AT(2)R-mediated mechanism. Estrogen can differentially regulate components of the RAS and is known to influence arterial pressure regulation. We hypothesized that AT(2)R-mediated depressor effects evident in females were estrogen dependent and thus would be abolished by ovariectomy and restored by estrogen replacement. Female Sprague-Dawley rats underwent ovariectomy or sham surgery and were treated with 17β-estradiol or placebo. Mean arterial pressure (MAP) was measured via telemetry in response to a 2-wk infusion of ANG II (50 ng·kg(-1)·min(-1) sc) or saline. MAP significantly decreased in females treated with ANG II (-10 ± 2 mmHg), a response that was abolished by ovariectomy (+4 ± 2 mmHg) and restored with estrogen replacement (-6 ± 2 mmHg). Cardiac and renal gene expression of components of the RAS was differentially regulated by estrogen, such that overall, estrogen shifted the balance of the RAS toward the vasodilatory axis. In conclusion, estrogen-dependent mechanisms offset the vasopressor actions of ANG II by enhancing RAS vasodilator pathways in females. This highlights the potential for these vasodilator pathways as therapeutic targets, particularly in women.