Induced fetal depressor or pressor responses associated with c-fos by intravenous or intracerebroventricular losartan.

ABSTRACT

Previous fetal studies have indicated depressor responses of intravenous (i.v.) administration of angiotensin antagonists. However, little is known of central effects of angiotensin blockers on fetal cardiovascular controlling. The cardiovascular effects of central administration of the angiotensin-1 (AT(1)) and angiotensin-2 (AT(2)) receptor antagonists, losartan and PD123319, were investigated in the chronically catheterized near-term ovine fetuses. Intravenous losartan produced within 1.5 min a significant and persistent depressor response [maximum Delta mean arterial pressure (MAP)=9 mm Hg] without altering fetal heart rate. Intracerebroventricular (i.c.v.) administration of losartan (1-5 mg/kg) increased fetal arterial pressures (Delta MAP=9-14 mm Hg). Central application of losartan (1 mg/kg) also increased fetal heart rate (maximum Delta heart rate=33 beat per minute). Losartan increased c-fos expression in the median preoptic nucleus and paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, the lateral parabrachial nuclei, and the ventrolateral medullabrain. These brain sectors are with abundant AT(1) receptors and have been demonstrated in the involvement in cardiovascular regulation. In contrast, intracerebroventricular injection of the AT(2) receptor antagonist PD123319 had no effect on fetal arterial pressure and heart rate. The results demonstrate strikingly functional differences of losartan on the fetal cardiovascular regulation in central and peripheral sides.