title: Endogenous angiotensin II has fewer effects but neuronal nitric oxide synthase has excitatory effects on renal sympathetic nerve activity in salt-sensitive hypertension-induced heart failure.
abstract: The effects of endogenous angiotensin II (Ang II) and neuronal nitric oxide synthase (nNOS) on tonic sympathetic activity were studied in salt-sensitive hypertension-induced heart failure. Dahl salt-sensitive rats were fed 8% NaCl diet for 9 weeks to induce chronic heart failure (CHF-DSS). The effects of intravenous administration of a selective nNOS inhibitor, S-methyl-L: -thiocitrulline (SMTC), and an Ang II type 1-receptor blocker, losartan, on renal sympathetic nerve activity (RSNA) were examined in chronically instrumented conscious rats. Baroreceptor (baro)-unloaded RSNA was obtained by decreasing arterial pressure with caval occlusion to determine tonic RSNA. SMTC significantly decreased baro-unloaded RSNA, and subsequent losartan recovered baro-unloaded RSNA to the control level in CHF-DSS rats. To compare the effects of the inhibitors between low- and high-activity states of the renin-angiotensin system (RAS), Sprague-Dawley rats were fed low (0.04%)- or high (8%)-salt diets. A significant difference was found in the effects of SMTC and/or losartan on RSNA between the high- and low-RAS states, which suggested that there is a difference in the effect of endogenous Ang II on RSNA between salt-induced and other-type heart failure. To examine the effects of heart failure on brain-tissue nNOS activity, we measured the activities of the diencephalon in heart-failure rats. Heart failure significantly suppressed diencephalon nNOS activity, which was significantly different from the results in salt-sensitive hypertension without heart failure. These results suggest that endogenous Ang II has fewer effects, but nNOS has excitatory effects on tonic RSNA in salt-sensitive hypertension-induced heart failure.
authors.affiliation: Department of Physiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. kemu@ndmc.ac.jp
authors.forename: Takehito
authors.initials: T
authors.lastname: Kemuriyama
authors.forename: Megumi
authors.initials: M
authors.lastname: Tandai-Hiruma
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sato
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishida