Effect of Central Losartan on DOCA-Salt Hypertension Rats

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 icvaCSF 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. Conclusions: 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 DOCAsalt hypertensive rat model. Losartan icv injection appeared to have a protective effect on the heart and kidney. (Korean Circulation J 2004;34 (1):84-91)