Cm. Santos et al., LOSARTAN IMPROVES BAROREFLEX CONTROL OF HEART-RATE OF COARCTED HYPERTENSIVE RATS, American journal of physiology. Heart and circulatory physiology, 38(3), 1995, pp. 812-818
To assess the role of angiotensin (ANG) II in both the increased heart
rate (HR) and the impaired baroreceptor reflex control of HR that cha
racterize the chronic phase of coarctation hypertension (CH), we compa
red basal HR, mean arterial pressure (MAP), and baroreflex sensitivity
of coarcted hypertensive rats treated chronically with losartan, capt
opril, or vehicle. Baseline HR was recorded daily, and MAP and reflex
HR changes and plasma renin activity (PRA) were measured in coarcted a
nd sham-coarcted rats on the 5th day after coarctation. Both captopril
(10 mg . kg(-1). day(-1) po) and losartan (10 mg kg-l day-l po) cause
d a small nonsignificant reduction of hypertension (132 +/- 5 and 133
+/- 5, respectively, vs. 147 +/- 9 mmHg in vehicle-treated rats), but
equally inhibited the late tachycardic phase (-37 +/- 13 and -29 +/- 1
2 beats/min in captopril- and losartan-treated groups, respectively, v
s. +79 +/- 19 beats/min in vehicle treated rats). Similar results were
obtained for other groups of coarcted hypertensive rats after suppres
sion of PRA by bilateral nephrectomy. Although hypertensive levels wer
e the same during both treatments, only losartan given orally or intra
cerebroventricularlly (1.25 mu g . kg(-1). h(-1)) was effective in imp
roving the reflex bradycardia. The depressed reflex tachycardia was co
rrected by chronic oral treatment with losartan. The data suggest that
the tachycardia occurring in the chronic phase of CH is mediated by b
lood-borne ANG II and that the normalization of the reflex control of
HR by losartan is achieved by blockade of type I receptors of ANG II i
n central areas accessible to oral or centrally administered losartan
but not to oral captopril.