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: Takehito Kemuriyama, Megumi Tandai-Hiruma, Kazuo Kato, Hiroyuki Ohta, Satoshi Maruyama, Yoshiaki Sato, Yasuhiro Nishida
• Journal: The journal of physiological sciences : JPS (J Physiol Sci) Vol. 59 Issue 4 Pg. 275-81 (Jul 2009) ISSN: 1880-6562 [Electronic] Japan
• PMID: 19340531 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Enzyme Inhibitors
• Sodium Chloride, Dietary
• Angiotensin II
• Citrulline
• Nitric Oxide
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type I
• Nos1 protein, rat
• Thiourea
• Losartan
• S-methylthiocitrulline

Topics

• Angiotensin II (physiology)
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Brain (enzymology)
• Citrulline (analogs & derivatives, pharmacology)
• Enzyme Inhibitors (pharmacology)
• Heart Failure (etiology, physiopathology)
• Hypertension (complications, physiopathology)
• Kidney (drug effects, innervation, physiology)
• Losartan (pharmacology)
• Male
• Nitric Oxide (physiology)
• Nitric Oxide Synthase (antagonists & inhibitors, physiology)
• Nitric Oxide Synthase Type I
• Pressoreceptors (physiopathology)
• Rats
• Rats, Inbred Dahl
• Renin-Angiotensin System (physiology)
• Sodium Chloride, Dietary (administration & dosage)
• Sympathetic Nervous System (drug effects, physiology)
• Thiourea (analogs & derivatives, pharmacology)