Expression of cyclooxygenase-2 in the macula densa of human kidney in hypertension, congestive heart failure, and diabetic nephropathy

Cyclooxygenase-2 (COX-2) is constitutively expressed in the macula densa of several laboratory animal species where it is considered to play a physiol ogic role in the regulation of basal renal function. Pertubations to normal homeostasis is shown to be associated with the upregulation of COX-2 in th e macula densa of rats and dogs. In contrast, COX-2 has not been detected i n the macula densa of normal adult human and non-human primate kidneys, sug gesting a less prominent role of this isoform in normal renal function in t hese species. In this study, we characterized COX-2 expression in human kid neys collected from subjects with a clinical history indicative of compromi sed renal function associated with diabetic nephropathy (DN), hypertension, and congestive heart failure (CHF). COX-2 expression was evaluated by immu nohistochemistry using isoform-specific antibodies and in situ hybridizatio n. No COX-2 protein or mRNA was observed in the macula densa of normal kidn eys (n = 11), whereas slight to moderate COX-2 expression was present in th e macula densa of 7/15 subjects (46%) with DN, 5/11 (46%) subjects with hyp ertension, and 3/10 subjects (30%) with CHF. These results indicate that CO X-2 is variably induced in the macula densa of the human kidney in compromi sed renal conditions and that COX-2-mediated prostaglandins may be involved in maintaining adequate renal functions in some patients with DN, hyperten sion, and CHF. This variability may be related to individual clinical statu s or synthesis of vasodilatory prostaglandins by cyclooxygenase-1 (COX-1).