Effect of in vivo gene transfer of nNOS in the PVN on renal nerve discharge in rats

Yi Fan Li, Shyamal K. Roy, Keith M. Channon, Irving H. Zucker, Kaushik P. Patel

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The paraventricular nucleus (PVN) of the hypothalamus is known to be involved in the control of sympathetic outflow. Nitric oxide (NO) has been shown to have a sympathoinhibitory effect in the PVN. The goal of the present study was to examine the influence of overexpression of neuronal NO synthase (nNOS) within the PVN on renal sympathetic nerve discharge (RSND). Adeno-virus vectors encoding either nNOS (Ad.nNOS) or β-galactosidase (Ad.β-Gal) were transfected into the PVN in vivo. Initially, the dose of adenovirus needed for infection was determined from in vitro infection of cultured fibroblasts. In Ad.nNOS-treated rats, the local expression of nNOS within the PVN was confirmed by histochemistry for NADPH-diaphorase-positive neurons. There was a robust increase in staining of NADPH-diaphorase-positive cells in the PVN on the side injected with Ad.nNOS. The staining peaked at 3 days after injection of the virus. In α-chloralose- and urethane-anesthetized rats, microinjection of NG-monomethyl-arginine (L-NMMA), a NO antagonist, into the PVN produced a dose-dependent increase in RSND, blood pressure, and heart rate. There was a potentiation of the increase in RSND, blood pressure, and heart rate due to L-NMMA in Ad.nNOS-injected rats compared with Ad.β-Gal-injected rats. These results suggest that the endogenous NO-mediated effect in the PVN of Ad.nNOS-treated rats is more effective in suppressing RSND compared with Ad.β-Gal-treated rats. These observations support the contention that an overexpression of nNOS within the PVN may be responsible for increased suppression of sympathetic outflow. This technique may be useful in pathological conditions know to have increased sympathetic outflow, such as hypertension or heart failure.

Original languageEnglish (US)
Pages (from-to)H594-H601
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number2 51-2
DOIs
StatePublished - 2002

Keywords

  • Neuronal nitric oxide synthase gene transfer
  • Paraventricular nucleus
  • Renal sympathetic nerve activity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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