Losartan improves baroreflex control of heart rate of coarcted hypertensive rats.
To assess the role of angiotensin (ANG) II in both the increased heart rate (HR) and the impaired baroreceptor reflex control of HR that characterize the chronic phase of coarctation hypertension (CH), we compared basal HR, mean arterial pressure (MAP), and baroreflex sensitivity of coarcted hypertensive rats treated chronically with losartan, captopril, or vehicle. Baseline HR was recorded daily, and MAP and reflex HR changes and plasma renin activity (PRA) were measured in coarcted and sham-coarcted rats on the 5th day after coarctation. Both captopril (10 mg.kg-1.day-1 po) and losartan (10 mg.kg-1.day-1 po) caused 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 +/- 12 beats/min in captopril- and losartan-treated groups, respectively, vs. +79 +/- 19 beats/min in vehicle treated rats). Similar results were obtained for other groups of coarcted hypertensive rats after suppression of PRA by bilateral nephrectomy. Although hypertensive levels were the same during both treatments, only losartan given orally or intracerebroventricularlly (1.25 micrograms.kg-1.h-1) was effective in improving the reflex bradycardia. The depressed reflex tachycardia was corrected by chronic oral treatment with losartan. The data suggest that the tachycardia occurring in the chronic phase of CH is mediated by blood-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 in central areas accessible to oral or centrally administered losartan but not to oral captopril.
Santos
C M
CM
Department of Physiology and Biophysics, University of São Paulo, Brazil.
Pontieri
V
V
Leomil Neto
M
M
Michelini
L C
LC
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001017:Aortic Coarctation / Q000150:complications*; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D002216:Captopril; D019808:Losartan