Nitric oxide synthase, ADMA, SDMA, and nitric oxide activity in the paraventricular nucleus throughout the etiology of renal wrap hypertension

Carrie A. Northcott, Scott Billecke, Teresa Craig, Carmen Hinojosa-Laborde, Kaushik P. Patel, Alex F. Chen, Louis G. D'Alecy, Joseph R. Haywood

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Within the paraventricular nucleus (PVN), there is a balance between the excitatory and inhibitory neurotransmitters that regulate blood pressure; in hypertension, the balance shifts to enhanced excitation. Nitric oxide (NO) is an atypical neurotransmitter that elicits inhibitory effects on cardiovascular function. We hypothesized that reduced PVN NO led to elevations in blood pressure during both the onset and sustained phases of hypertension due to decreased NO synthase (NOS) and increased asymmetrical dimethylarginine (ADMA; an endogenous NOS inhibitor) and symmetric dimethylarginine (SDMA). Elevated blood pressure, in response to PVN bilateral microinjections of a NO inhibitor, nitro-L-arginine methyl ester, was blunted in renal wrapped rats during the onset of hypertension (day 7) and sustained renal wrap hypertension (day 28) compared with sham-operated rats. Adenoviruses (Ad) encoding endothelial NOS (eNOS) or LacZ microinjected into the PVN [1 × 10 9 plaque-forming units, bilateral (200 n1/site)] reduced mean arterial pressure compared with control (Day 7, Ad LacZ wrap: 144 ± 7 mmHg and Ad eNOS wrap: 117 ± 5 mmHg, P 0.05) throughout the study udy (Day 28, Ad LacZ wrap: 123 ± 1 mm Hg and Ad eNOS wrap: 108 ± 4 mmHg, P 0.05). Western blot analyses of PVN NOS revealed significantly lower PVN neuronal NOS during the onset of hypertension but not in sustained hypertension. Reduced SDMA was found in the PVN during the onset of hypertension; however, no change in ADMA was observed. In conclusion, functional indexes of NO activity indicated an overall downregulation of NO in renal wrap hypertension, but the mechanism by which this occurs likely differs throughout the development of hypertension.

Original languageEnglish (US)
Pages (from-to)H2276-H2284
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume302
Issue number11
DOIs
StatePublished - Jun 1 2012

Keywords

  • Asymmetrical dimethylarginine
  • Gene transfer
  • Neurotransmission
  • Symmetrical dimethylarginine

ASJC Scopus subject areas

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

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