Response of cardiac sympathetic nerve activity to intravenous irbesartan in heart failure

Abstract

To determine the effect of irbesartan treatment on resting levels and arterial baroreflex control of cardiac sympathetic nerve activity (CSNA) in heart failure (HF), we studied conscious normal sheep and sheep with HF induced by rapid ventricular pacing for 8-10 wk (n = 7 per group). In HF, there is a large increase in CSNA that is detrimental to outcome. The causes of this increase in CSNA and the effect of angiotensin receptor blockers on CSNA in HF are unclear. CSNA, arterial blood pressure, heart rate (HR), and arterial baroreflex curves were recorded during a resting period and after 90 min of irbesartan infusion (12 mg.kg(-1).h(-1) iv). This dose of irbesartan abolished the pressor response to intravenous ANG II infusion but caused only a slight decrease in the pressor response to centrally administered ANG II. In HF, there was a large increase in CSNA (from 44 +/- 3 to 87 +/- 3 bursts/100 heartbeats). Irbesartan reduced arterial pressure in the normal and HF groups, but the usual baroreflex-mediated increases in CSNA and HR were prevented. This resulted from a significant leftward shift in the CSNA and HR baroreflex curves in both groups. Irbesartan also decreased the sensitivity of the arterial baroreflex control of CSNA. Short-term treatment with an angiotensin receptor blocker, at a dose that abolished the response to circulating, but not central, ANG II, prevented the reflex increase in CSNA in response to the drug-induced fall in arterial pressure.

Fig. 1.

Recordings of arterial pressure (AP), cardiac sympathetic nerve activity (CSNA), and cardiac nerve (CN) spikes in a conscious normal sheep and a sheep in heart failure (HF). Note much higher burst incidence of CSNA in the HF than in the normal sheep.

Fig. 2.

Resting levels of diastolic blood pressure (dBP), heart rate, CSNA, and CSNA burst incidence recorded in conscious normal and HF sheep during the control period (C) and after 90 min of irbesartan (Irb) infusion. Values are means ± SE (n = 7 in both groups). *P < 0.05 vs. normal. #P < 0.05 within groups (C vs. Irb).

Fig. 3.

Arterial baroreflex curves for CSNA and heart rate (HR) during the control period (solid line, black circles) and after intravenous infusion of irbesartan (dashed line, white circles) in normal and HF sheep. CSNA is presented as percentage of maximum activity measured when arterial pressure was reduced with sodium nitroprusside. Resting points were taken from 5 min of recording during control periods. Values are means ± SE (n = 7 in both groups).