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Prevention of sympathetic hyperactivity in rats with CHF post‐MI by chronic subcutaneous administration of losartan
Author(s) -
Huang Bing S,
Ahamad Monir,
Leenen Frans HH
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1204-c
Subject(s) - losartan , medicine , baroreflex , phenylephrine , blockade , angiotensin ii , endocrinology , anesthesia , blood pressure , heart rate , receptor
In rats post‐MI, sympathetic hyperactivity and LV dysfunction are attenuated by central AT 1 receptor blockade with icv infusion of losartan at doses which are ineffective when administered peripherally. The present study tested whether post‐MI peripheral administration of losartan can have similar effects as icv infusion. Wistar rats as of 2 days after coronary artery ligation were injected sc daily with losartan at a low or high dose (15 or 100 mg/kg/d), or vehicle. Rats with sham ligation served as control. After 4 wk, MAP, HR, renal sympathetic nerve activity (RSNA) were recorded at rest and in response to air‐jet stress and iv phenylephrine and nitroprusside for baroreflex function. Cardiac function was assessed with a Millar catheter in LV.MI size was similar for 3 MI groups. Losartan at low dose ameliorated and at high dose prevented sympathetic hyperactivity. Losartan at both doses improved LVEDP but further decreased LVPSP, and decreased dp/dt max at high dase post MI. Thus, sc losartan at high doses can prevent sympathetic hyperactivity likely through blockade of AT 1 receptors in the brain. However, it results in hypotension and is less effective than central AT 1 blockade in preventing LV dysfunction.