Treatment with Losartan Improves Baroreflexes in Obese Zucker Rats Coincident with Enhanced Response of Nucleus Tractus Solitarius (NTS) to Increased Arterial Pressure




Chaudhary, Parul
Schreihofer, Ann
Dohi, Akiko


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Obese Zucker rats (OZR) have impaired baroreflex-mediated responses to acute rises in mean arterial pressure (MAP) coincident with the development of hypertension. In addition, the NTS becomes less responsive, with reduced phenylephrine (PE)-induced c-Fos expression and smaller physiological responses to glutamate in the NTS. Here, we determined if treatment with the angiotensin- AT1 receptor antagonist, losartan (LOS) improves baroreflexes and the PE-induced c-Fos expression in NTS of OZR. Baroreflex-mediated changes in HR to PE-evoked rises in MAP (40 mmHg) were measured in conscious rats implanted with femoral catheters. Rises in MAP were sustained with PE, and then rats were perfused after 90 min to examine NTS c-Fos expression. Treatment with LOS (for 5 wks) normalized MAP in OZR vs. LZR (untreated: 128±2 vs. 115±3 mmHg, with LOS: 111±3 vs. 112±2 mmHg; at 14.1 wks). LOS treatment enhanced PE-induced reductions in HR in OZR but not LZR. (untreated: 43±10 vs. -101±9 -bpm; with LOS: . -75±12 vs. -112±11bpm). Although LOS improved PE-induced reductions in HR in OZR, responses in LOS-treated OZR were still smaller vs. LOS-treated LZR, suggesting a partial restoration of baroreflexes. PE-induced c-Fos expression in NTS was less in untreated OZR vs. LZR (30±5 vs. 50±6 counts). Treatment with LOS enhanced PE-induced c-Fos expression in OZR (54±11 counts), but not LZR (58±11 counts), rendering comparable PE-induced c-Fos expression in LOS-treated OZR and LZR. These data suggest that LOS improves hypertension, baroreflexes, and NTS function in OZR. Further study is needed to determine whether improved function by LOS is explained by normalization of MAP in OZR.