Effect of Central Losartan on DOCA-Salt Hypertension Rats

Abstract

BACKGROUND: The purpose of this study was to investigate whether brain AT1 receptor stimulation contributes as a hypertensive mechanism to deoxycorticosterone acetate (DOCA)-salt hypertension.

METHODS: 1) Acute injection:Losartan (1 mg/4 uL) or artificial cerebrospinal fluid (aCSF) was injected into the lateral cerebral ventricle (icv) of conscious control uninephrectomized Wistar rats or rats with DOCA-salt at 2 or 4 weeks, and mean arterial pressure (MAP) and heart rates (HR) were recorded. 2) Chronic injection:Using osmotic minipump, losartan (1 mg/kg/d) or aCSF was injected to a sham group or three DOCA-salt rat groups [icv-aCSF, icv-losartan, sc-losartan (subcutaneous) groups] for 4 weeks, after which the MAP and HR were recorded in addition to the weights of the left (LV) and right ventricles (RV) and kidneys.

RESULTS: 1) Acute injection: In rats treated with DOCA-salt, resting MAP significantly increased compared to the control group [144±6 mmHg (2 weeks), 170±5 mmHg (4 weeks) vs 115-120 mmHg (controls)]. MAP decreased significantly (2 weeks, 4 weeks) at 4, 8, 24 hours after icv injection of losartan to the level of the control group. 2) Chronic injection: The general trend showed that MAP decreased more in the icv-losartan group than in the icv-aCSF group (127±15.2 mmHg vs 141.1±5.5 mmHg, p=0.0578). In all DOCA-salt groups, no differences in RV weight were found. In the icv-aCSF and sclosartan groups, the kidney weight increased compared to the control group, but there was no difference in LV and kidney weight between the icv-losartan group and the control group.

CONCLUSION: Normalization of MAP after acute or chronic icv administration of the AT1 receptor antagonist suggests that the stimulation of the brain AT1 receptor plays a significant role in the development and maintenance of hypertension in the DOCA-salt hypertensive rat model. Losartan icv injection appeared to have a protective effect on the heart and kidney.