PMID- 9933253
OWN - NLM
STAT- MEDLINE
DCOM- 19990304
LR  - 20191210
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 84
IP  - 2
DP  - 1999 Feb 5
TI  - Mechanism of nitric oxide-induced vasodilatation: refilling of intracellular 
      stores by sarcoplasmic reticulum Ca2+ ATPase and inhibition of store-operated 
      Ca2+ influx.
PG  - 210-9
AB  - The precise mechanisms by which nitric oxide (NO) decreases free [Ca2+]i, 
      inhibits Ca2+ influx, and relaxes vascular smooth muscle are poorly understood. 
      In rabbit and mouse aorta, agonist-induced contractions and increases in [Ca2+]i 
      were resistant to nifedipine, suggesting Ca2+ entry through non-L-type Ca2+ 
      channels. Relaxations to NO were inhibited by thapsigargin (TG) or cyclopiazonic 
      acid (CPA) indicating the involvement of sarcoplasmic reticulum ATPase (SERCA). 
      Studies of the effect of NO on [Ca2+]i and the rate of Mn2+ influx with fura-2 
      fluorometry in rabbit aortic smooth muscle cells in primary culture were designed 
      to test how SERCA is involved in mediating the response to NO. When cells were 
      stimulated with angiotensin II (AII), NO accelerated the removal of Ca2+ from the 
      cytoplasm, decreased [Ca2+]i, and inhibited Ca2+ and Mn2+ influx. Inhibition of 
      SERCA abolished all the effects of NO. In contrast, inhibition of the 
      Na+/Ca2+exchanger or the plasma membrane Ca2+ ATPase had no influence on the 
      ability of NO to decrease [Ca2+]i. NO maximally decreased [Ca2+]i within 5 s, 
      whereas significant inhibition of AII-induced Ca2+ and Mn2+ influx required more 
      than 15 s. The inhibition of cation influx strictly depended on [Ca2+]o and 
      functional SERCA, suggesting that during the delay before NO inhibits Ca2+ 
      influx, the influx of Ca2+ and the uptake into intracellular stores are required. 
      In the absence of [Ca2+]o, NO diminished the AII-induced [Ca2+]i transient by a 
      SERCA-dependent mechanism and increased the amount of Ca2+ in the stores 
      subsequently released by ionomycin. The present study indicates that the initial 
      rapid decrease in [Ca2+]i caused by NO in vascular smooth muscle is accounted for 
      by the uptake of Ca2+ by SERCA into intracellular stores. It is proposed that the 
      refilling of the stores inhibits store-operated Ca2+ influx through non-L-type 
      Ca2+ conducting ion channels and that this maintains the decrease in [Ca2+]i and 
      NO-induced relaxation.
FAU - Cohen, R A
AU  - Cohen RA
AD  - Vascular Biology Unit, Whitaker Cardiovascular Institute, Evans Department of 
      Clinical Research, Department of Medicine, Boston University Medical Center, 
      Boston, MA, USA. racohen@med-med1.bu.edu
FAU - Weisbrod, R M
AU  - Weisbrod RM
FAU - Gericke, M
AU  - Gericke M
FAU - Yaghoubi, M
AU  - Yaghoubi M
FAU - Bierl, C
AU  - Bierl C
FAU - Bolotina, V M
AU  - Bolotina VM
LA  - eng
GR  - HL31607/HL/NHLBI NIH HHS/United States
GR  - HL54150/HL/NHLBI NIH HHS/United States
GR  - HL55620/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 11128-99-7 (Angiotensin II)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - I9ZF7L6G2L (Nifedipine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Aorta, Thoracic/cytology/metabolism
MH  - Calcium/*metabolism
MH  - Calcium-Transporting ATPases/*metabolism
MH  - Homeostasis
MH  - Mice
MH  - Muscle, Smooth/cytology/metabolism
MH  - Nifedipine/pharmacology
MH  - Nitric Oxide/*physiology
MH  - Rabbits
MH  - Sarcoplasmic Reticulum/*enzymology
MH  - Vasodilation/*physiology
EDAT- 1999/02/05 00:00
MHDA- 1999/02/05 00:01
CRDT- 1999/02/05 00:00
PHST- 1999/02/05 00:00 [pubmed]
PHST- 1999/02/05 00:01 [medline]
PHST- 1999/02/05 00:00 [entrez]
AID - 10.1161/01.res.84.2.210 [doi]
PST - ppublish
SO  - Circ Res. 1999 Feb 5;84(2):210-9. doi: 10.1161/01.res.84.2.210.