Losartan Injected into the Nucleus of the Solitary Tract Blunts Pressor Mechanisms Activated by High‐Fat Diet

Abstract

High‐fat diet (HFD) increases the activity of renin‐angiotensin system, sympathetic nerve activity (SNA) and arterial pressure. In the present study, we evaluated the cardiovascular changes produced by HFD in rats treated with angiotensin type 1 receptor (AT1r) blocker injected into the nucleus of the solitary tract (NTS). Male Holtzman rats (300‐320 g, n = 5‐6/group) with stainless steel guide‐cannulas implanted into the NTS were fed with either standard rat chow diet (SD; 5.4% total fat) or HFD (26.4% total fat) for 6 weeks. Mean arterial pressure (MAP), heart rate (HR) and the low frequency (LF) of the systolic blood pressure (SBP, an index of vasomotor SNA) were evaluated in conscious rats, before and after bilateral microinjections of losartan (AT1r antagonist, 10 μg/100 nl) into the NTS. HFD rats presented an increased MAP (115 ± 2 vs. SD: 105 ± 2 mmHg, p < 0.05) and LF of the SBP (9.3 ± 0.9 vs. SD: 4.9 ± 0.6 mmHg2, p < 0.05). Losartan injected into the NTS reduced MAP and LF of SBP (respectively, 107 ± 2 mmHg and 6.6 ± 1.0 mmHg2 vs. baseline pre‐injection; p < 0.05) in HFD rats, but not in SD rats (102 ± 4 mmHg and 4.7 ± 1.0 mmHg2, p > 0.05). Losartan into the NTS in HFD or SD rats produced no significant changes in HR. These results suggest that AT1r in the NTS acts increasing MAP and sympathetic modulation of arterial pressure in HFD rats.