PMID- 20096684
OWN - NLM
STAT- MEDLINE
DCOM- 20100517
LR  - 20231213
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 631
IP  - 1-3
DP  - 2010 Apr 10
TI  - Improvement of impaired endothelial function by tetrahydrobiopterin in 
      stroke-prone spontaneously hypertensive rats.
PG  - 28-35
LID - 10.1016/j.ejphar.2010.01.003 [doi]
AB  - To investigate the role of tetrahydrobiopterin (BH4), an essential cofactor of 
      nitric oxide synthase, in endothelial function in a model of genetic 
      hypertension, acetylcholine- and sodium nitroprusside (SNP)-induced vasodilator 
      responses were examined in the absence and presence of BH4 in age-matched adult 
      stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. 
      Acetylcholine-induced depressor responses attenuated significantly in SHRSP 
      compared with those in WKY rats. Acetylcholine-induced relaxations in 
      phenylephrine-precontracted aortic rings of SHRSP were also significantly 
      impaired as compared to those of WKY rats, while SNP-induced relaxations were 
      similar between both strains. In SHRSP, intravenous infusion of BH4 (0.12 mg/kg 
      per min for 20 min following a bolus injection of 0.48 mg/kg) significantly 
      improved vasodilator responses to acetylcholine without affecting those to SNP, 
      but in WKY rats BH4 did not influence those to acetylcholine. BH4 infusion itself 
      had no hemodynamic effect in both strains. However, BH4 levels in plasma and 
      thoracic aorta as well as plasma concentrations of nitrite plus nitrate, 
      metabolites of NO, in SHRSP were all significantly greater than those in WKY 
      rats, suggesting the occurrence of compensatory upregulation of NO synthesis in 
      SHRSP. These results demonstrate that the impaired endothelial function in SHRSP 
      cannot be explained simply by the decrease in absolute amount of BH4.
CI  - Copyright (c) 2009 Elsevier B.V. All rights reserved.
FAU - Noguchi, Katsuhiko
AU  - Noguchi K
AD  - Department of Pharmacology, School of Medicine, Faculty of Medicine, University 
      of the Ryukyus, Okinawa 903-0215, Japan. noguchi@med.u-ryukyu.ac.jp
FAU - Hamadate, Naobumi
AU  - Hamadate N
FAU - Matsuzaki, Toshihiro
AU  - Matsuzaki T
FAU - Sakanashi, Mayuko
AU  - Sakanashi M
FAU - Nakasone, Junko
AU  - Nakasone J
FAU - Sakanashi, Makiko
AU  - Sakanashi M
FAU - Tsutsui, Masato
AU  - Tsutsui M
FAU - Sakanashi, Matao
AU  - Sakanashi M
LA  - eng
PT  - Journal Article
DEP - 20100121
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Vasoconstrictor Agents)
RN  - 0 (Vasodilator Agents)
RN  - 0 (Biopterins)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EGX657432I (sapropterin)
SB  - IM
MH  - Animals
MH  - Aorta, Abdominal/drug effects/*physiopathology
MH  - Aorta, Thoracic/drug effects/metabolism
MH  - Biopterins/administration & dosage/*analogs & 
      derivatives/blood/metabolism/physiology
MH  - Dietary Supplements
MH  - Endothelium, Vascular/drug effects/*physiopathology
MH  - Hemodynamics/drug effects
MH  - Hypertension/genetics/*physiopathology
MH  - In Vitro Techniques
MH  - Infusions, Intravenous
MH  - Male
MH  - Nitrates/blood
MH  - Nitric Oxide Synthase/antagonists & inhibitors
MH  - Nitrites/blood
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Time Factors
MH  - Vasoconstrictor Agents/pharmacology
MH  - *Vasodilation/drug effects
MH  - Vasodilator Agents/pharmacology
EDAT- 2010/01/26 06:00
MHDA- 2010/05/18 06:00
CRDT- 2010/01/26 06:00
PHST- 2009/07/18 00:00 [received]
PHST- 2009/12/04 00:00 [revised]
PHST- 2010/01/12 00:00 [accepted]
PHST- 2010/01/26 06:00 [entrez]
PHST- 2010/01/26 06:00 [pubmed]
PHST- 2010/05/18 06:00 [medline]
AID - S0014-2999(10)00040-3 [pii]
AID - 10.1016/j.ejphar.2010.01.003 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2010 Apr 10;631(1-3):28-35. doi: 10.1016/j.ejphar.2010.01.003. 
      Epub 2010 Jan 21.