The diuretic chlorthalidone normalizes baroreceptor and Bezold-Jarisch reflexes in DOCA-salt hypertensive rats

The contributions of arterial baroreceptor and Bezold-Jarisch reflexes, and atrial natriuretic factor (ANF) to the anti-hypertensive effect of the diu retic chlorthalidone were investigated in rats with deoxycorticosterone ace tate (DOCA)-salt-induced hypertension. Chlorthalidone (8 mg rat(-1) day(-1) added to food) was given to one group during all 20 days of DOCA (8 mg kg( -1) s.c. twice per week) administration (preventive regimen) and, to anothe r group, 20 days after DOCA treatment was initiated until the 40th day (the rapeutic regimen). DOCA caused a significant increase in mean arterial pres sure, reduced arterial baroreflex, and increased both the Bezold-Jarisch re flex and pro-ANF converting enzyme activity. Chlorthalidone reversed or pre vented the DOCA-salt-induced hypertension, which was accompanied by the nor malization of both the arterial baroreflex and the Bezold-Jarisch reflex. A dditionally, both preventive and therapeutic regimens with chlorthalidone d id cause normalization of the plasma sodium concentration and pro-ANF conve rting enzyme activity in the left atrium that follows DOCA-salt hypertensio n. Although it is difficult to determine the relative importance of each of the above regulatory mechanisms altered by chlorthalidone treatment, these data indicate that they may account for the prevention or decrease of DOCA -salt-induced hypertension in rats. (C) 2000 Academic Press.