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Conclusions  The C4B*Q0 genotype may be associated with hyperreactivity of the HPA axis (manifested as an increased responsiveness to ACTH-stimulation), probably through enhanced function of steroid 21-hydroxylase. Since hyperreactivity of the HPA axis is known to be associated with an increased risk of cardiovascular disease, our present findings may explain the increased cardiovascular morbidity and mortality of C4B*Q0 carriers.

We next studied the effects of the selective MR antagonist eplerenone and the angiotensin II receptor blocker candesartan on motor and sensory nerve conduction velocity (NCV) and morphometric changes and cyclooxygenase-2 (COX-2) gene and NF-κB protein expression in the peripheral nerves of STZ-induced diabetic rats. Expression of MR protein and mRNA in peripheral nerves was equal to that in the kidney. Motor NCV was significantly improved by 8 weeks of treatment with either eplerenone (39.1 ± 1.2 m/s) or candesartan (46.4 ± 6.8 m/s) compared to control diabetic rats (33.7 ± 2. m/s) (p<.5). Sensory NCV was also improved by treatment with candesartan or eplerenone in diabetic rats. Eplerenone and candesartan caused significant improvement in mean myelin fiber area and mean myelin area compared with control diabetic rats (p<.5). COX-2 mRNA and NF-κB protein were significantly elevated in the peripheral nerves of diabetic rats compared with control rats, and treatment with eplerenone or candesartan reduced these changes in gene expression (p<.5).MR blockade may have neuroprotective effects on diabetic peripheral neuropathy.