PMID- 10690284
OWN - NLM
STAT- MEDLINE
DCOM- 20000313
LR  - 20190513
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 44
IP  - 3
DP  - 1999 Dec
TI  - Hemodynamic effects of nitric oxide synthase inhibition at steady state and 
      following tumor necrosis factor-alpha-induced myodepression.
PG  - 527-35
AB  - OBJECTIVE: Nitric oxide (NO) has been proposed as a common mediator of tumor 
      necrosis factor-alpha (TNF alpha)-induced vasodilation and myocardial 
      dysfunction. Accordingly, we performed an extensive assessment of the influence 
      of NO synthase inhibition on left ventricle (LV) and circulatory performance in 
      conscious dogs at steady state and after establishment of TNF alpha mediated 
      myodepression. METHODS: Autonomically blocked, chronically instrumented dogs were 
      studied at steady state and 6 h after initiation of a 1-h rhTNF alpha infusion 
      (40 micrograms/kg). Ventricular performance was evaluated using the 
      pressure-volume framework. Dogs were then treated with either NG-nitro-L-arginine 
      methylester (L-NAME, 40 mg/kg bolus) or angiotensin II (250-500 ng/kg). RESULTS: 
      L-NAME, under control conditions or following recombinant human (rh) TNF 
      alpha-induced ventricular dysfunction, produced marked increases in afterload 
      with attendant increases in LV pressure, volume, and prolonged isovolumic 
      relaxation without adversely influencing coronary blood flow. regardless of 
      whether the dogs received rhTNF alpha, L-NAME did not affect the slopes of the 
      end-systolic pressure-volume and stroke-work (SW)-end-diastolic volume (EDV) 
      relations (force-based measure of contractility), whereas the slope of the 
      dP/dtmax-EDV relation, a velocity dependent parameter of LV systolic function, 
      declined. Overall ventricular performance, as seen by the circulation, was 
      reduced by L-NAME in control as well as rhTNF alpha-treated dogs, evidenced by 
      rightward shifts of the SW-EDV and dP/dtmax-EDV relations. Similar findings were 
      observed in the separate cohorts of dogs, at steady state and 6 h after rhTNF 
      alpha, following angiotensin II at matched systolic pressure. CONCLUSIONS: 
      Systemic NO synthase inhibition with L-NAME does not acutely reverse rhTNF 
      alpha-induced myocardial dysfunction. The detrimental influence of L-NAME on LV 
      size, relaxation, and velocity-based measures of contractility is likely 
      attributable to its effects on increasing afterload.
FAU - Murray, D R
AU  - Murray DR
AD  - Department of Medicine, University of Texas Health Science Center at San Antonio 
      78284, USA.
FAU - Prabhu, S D
AU  - Prabhu SD
FAU - Freeman, G L
AU  - Freeman GL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Analysis of Variance
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Dogs
MH  - Enzyme Inhibitors/*pharmacology
MH  - Female
MH  - Hemodynamics/*drug effects
MH  - Male
MH  - Myocardial Contraction/*drug effects
MH  - NG-Nitroarginine Methyl Ester/*pharmacology
MH  - Nitric Oxide Synthase/*antagonists & inhibitors
MH  - Stroke Volume/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Ventricular Pressure/drug effects
EDAT- 2000/02/26 09:00
MHDA- 2000/03/18 09:00
CRDT- 2000/02/26 09:00
PHST- 2000/02/26 09:00 [pubmed]
PHST- 2000/03/18 09:00 [medline]
PHST- 2000/02/26 09:00 [entrez]
AID - S0008636399002266 [pii]
AID - 10.1016/s0008-6363(99)00226-6 [doi]
PST - ppublish
SO  - Cardiovasc Res. 1999 Dec;44(3):527-35. doi: 10.1016/s0008-6363(99)00226-6.