Regulation of sympathetic nerve activity and arterial pressure by the rostral ventrolateral medulla in obese Zucker rats.

Abstract

Adult obese Zucker rats (OZR) have elevated sympathetic nerve activity (SNA) and arterial pressure (AP) with exaggerated sympatho‐excitatory responses (somatic and diving reflex) compared to lean Zucker rats (LZR). The present study sought to determine whether the altered control of SNA and AP in OZR could be due to enhanced glutamatergic or reduced GABAergic control of the rostral ventrolateral medulla (RVLM). Adult rats (14‐17 wks) were anesthetized with urethane (1.5 g/kg, iv), ventilated, and paralyzed for recording of SNA and AP. Microinjections of glutamate (1 nmol/100 nl) were performed into the RVLM to locate sites for maximal increases in SNA and AP (1.4 ‐ 1.8 mm rostral to calamus, 1.7 ‐ 2.1 mm lateral to midline, 2.7 ‐ 3.1 mm ventral; tip angled 20° rostrally). Baseline mean AP of OZR was significantly higher than LZR (n=6, 124 ± 2 mmHg in OZR vs n=6, 108 ± 6 mmHg in LZR, P<0.05). The OZR had larger maximal increases in AP (n=6, 30 ± 3 mmHg in OZR vs n=6, 20 ± 2 mmHg in LZR, P<0.05) and SNA (n=6, 74 ± 8 % of baseline in OZR vs n=6, 58 ± 8 % in LZR) than LZR. After the blockade of GABAA receptors in the RVLM (gabazine; 100 pmol/100nl) the increases in AP (n=6, 58 ± 11 mmHg in OZR vs n=6, 42 ± 7 mmHg in LZR) and SNA (n=6, 83 ± 17 % of baseline in OZR vs n=6, 84 ± 21 % in LZR) were similar between groups. These results suggest that the RVLM is more easily activated by glutamate, but that tonic GABAergic inhibition of the RVLM is not altered in OZR compared to LZR.Grant Support: NIH R01HL086759