Altered effects of angiotensin ii type 1 and type 2 receptor blockers on cardiac norepinephrine release and inotropic responses during cardiac sympathetic nerve stimulation in aorto-caval shunt rats.

摘要

BACKGROUND: Inhibition of the sympathetic nervous and renin - angiotensin systems has become an important strategy in the treatment of chronic heart failure. However, direct evidence of how inhibition of the renin - angiotensin system alters sympathetic activity in a diseased heart is lacking. METHODS AND RESULTS: Four weeks after abdominal aorto-caval (AV) shunting or sham operation in rats, the hearts were retrogradely perfused in vivo and the left ventricles contracted isovolumetrically at 300 beats/min. Sympathetic nerve stimulation (SNS) was performed in the baseline state and repeated with an infusion of the angiotensin II (A-II) type 1 receptor (AT(1)-R) blocker, losartan, the A-II type 2 receptor (AT(2)-R) blocker, PD123319, or A-II. Norepinephrine (NE) overflow and left ventricular (LV) inotropic responses during baseline SNS were lower in the AV shunt rats. Losartan did not change the NE overflow or the LV inotropic responses to SNS in the sham rats, but did increase them in the AV shunt rats. PD123319 changed neither parameter in the sham rats, but decreased both in the AV shunt rats. A-II enhanced the NE overflow but attenuated the LV inotropic responses to SNS in the sham rats, but attenuated both in the AV shunt rats. CONCLUSIONS: The effects of A-II via the AT(1)-R and AT(2)-R on the adrenergic drive in the heart were altered significantly in volume overload hypertrophy induced by AV shunting.