Abstract
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. 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. The effects of A-II via the ...Continue Reading
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