The ECS is expressed throughout the kidney. AEA systemically resulted in vasodilation of the efferent and afferent arterioles with a decrease in GFR. This vasodilation was mediated by CB1 receptor-activated production of NO. Activation of CB1 receptor in mice also increased protein secretion and resulted in proteinuria. A small study in humans showed increased levels of CB1 expression in patients with IgA nephropathy, diabetic nephropathy, and acute interstitial nephritis, mainly in endothelial cells but also in tubules, interstitial cells, and podocytes in diabetic nephropathy. CB1 receptor expression in the renal tissue is also dramatically increased after unilateral obstruction of the ureter. This leads to increased fibrosis with increased expression of CB1 in myofibroblasts. CB2 receptor activation under the same experimental conditions decreased fibrosis, although the exact mechanism is unknown. In the case of acute kidney injury (AKI) due to ischemic insults, both CB1 and CB2 have shown benefit in preventing injury when administered prior to ischemia, with CB2 also playing a protective role in AKI due to cisplatin nephropathy and ischemic insult. ECS levels in various chronic disease states are mixed with patients with autosomal dominant polycystic kidney disease (ADPKD) having a relative ECS deficiency, and patients with higher 2-AG levels maintaining better renal function, while ESRD patients were found to have higher 2-AG levels than healthy controls. Rat studies indicate a protective function of the ECS in hypertensive kidney disease. CB1, CB2, and TRPV1 are also found in the bladder and decrease bladder pain and spasm. Low levels of AEA have been identified in patients with interstitial cystitis, possibly representing another ECS deficiency syndrome.