Blockade of mineralocorticoid receptors in the dorsal hindbrain enhances baroreflex sensitivity (1130.4)

Abstract

This study tested the hypothesis that chronic blockade of mineralocorticoid receptors (MR) in the dorsal hindbrain (DBH) enhances spontaneous baroreflex sensitivity (sBRS) in male Sprague‐Dawley rats subjected to chronic variable stress (CVS) for 2 weeks. Rats were instrumented with radiotelemetry transmitters to obtain cardiovascular data, and pellets made of cholesterol (Chol) or the MR antagonist spironolactone (SPL) were implanted on the DBH (n=5‐6 per group). Two weeks later rats were subjected to CVS, which included insulin‐induced hypoglycemia on the first day of stress. SPL significantly (P<0.05) increased the sBRS prior to (2.1±0.1 vs. 1.5±0.2 ms/mmHg in SPL vs Chol rats) and after 2 weeks of CVS (2.1±0.1 vs. 1.6±0.2 ms/mmHg in SPL vs Chol rats). Neither CVS nor hypoglycemia altered sBRS. Blood glucose was measured at 20, 40, 60, 90, 120 and 180 min after insulin (7‐8 U/kg, i.p.) was administered to non‐fasted rats. Glucose reached a nadir at 2 hr, when levels were significantly higher in SPL compared to Chol rats, (37±3 vs.28±1 mg/dl, P<0.05). The results indicate that chronic blockade of DHB MR enhances sBRS and blunts the hypoglycemic effect of insulin.Grant Funding Source: Supported by NIH #HL076807 and AHA #GRNT4460047