Effect of chemical inhibition or ablation of the paraventricular nucleus of the hypothalamus on cardiac sympathetic nerve activity in heart failure

摘要: There is convincing evidence that sympathoexcitation in heart failure (HF) is partly centrally mediated, but the sites driving the increased cardiac sympathetic nerve activity (CSNA) are unknown. As the paraventricular nucleus of the hypothalamus (PVN) has been proposed to play a role in driving the renal sympathoexcitation in HF, we investigated whether it also mediates the cardiac sympathoexcitation. In conscious sheep with pacing‐induced HF, CSNA was dramatically increased compared with normal sheep (34 ± 5 to 93 ± 2 bursts/100 heart beats). In HF, microinjection of glycine (250 nmol in 500 nl) bilaterally into the PVN had no effect on the elevated CSNA or on the arterial baroreflex control of CSNA or heart rate. In normal sheep, PVN microinjection of glycine did not change basal CSNA, but decreased the range of the heart rate baroreflex curve (161 ± 8 to 132 ± 4 bpm, p<0.05). In a further 5 HF sheep …