cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation
Paolocci, N ; Ekelund, Ulf LU
; Isoda, T
; Ozaki, M
; Vandegaer, K
; Georgakopoulos, D
; Harrison, R W
; Kass, D A
and Hare, J M
(2000)
In American Journal of Physiology: Heart and Circulatory Physiology
279(4).
p.1982-1988
- Abstract
- Nitric oxide (NO) has concentration-dependent biphasic myocardial contractile effects. We tested the hypothesis, in isolated rat hearts, that NO cardiostimulation is primarily non-cGMP dependent. Infusion of 3-morpholinosydnonimine (SIN-1, 10(-5) M), which may participate in S-nitrosylation (S-NO) via peroxynitrite formation, increased the rate of left ventricular pressure rise (+dP/dt; 19 +/- 4%, P < 0.001, n = 11) without increasing effluent cGMP or cAMP. Superoxide dismutase (SOD; 150 U/ml) blocked SIN-1 cardiostimulation and led to cGMP elaboration. Sodium nitroprusside (10(-10)-10(-7) M), an iron nitrosyl compound, did not augment +dP/dt but increased cGMP approximately eightfold (P < 0.001), whereas diethylamine/NO (DEA/NO;... (More)
- Nitric oxide (NO) has concentration-dependent biphasic myocardial contractile effects. We tested the hypothesis, in isolated rat hearts, that NO cardiostimulation is primarily non-cGMP dependent. Infusion of 3-morpholinosydnonimine (SIN-1, 10(-5) M), which may participate in S-nitrosylation (S-NO) via peroxynitrite formation, increased the rate of left ventricular pressure rise (+dP/dt; 19 +/- 4%, P < 0.001, n = 11) without increasing effluent cGMP or cAMP. Superoxide dismutase (SOD; 150 U/ml) blocked SIN-1 cardiostimulation and led to cGMP elaboration. Sodium nitroprusside (10(-10)-10(-7) M), an iron nitrosyl compound, did not augment +dP/dt but increased cGMP approximately eightfold (P < 0.001), whereas diethylamine/NO (DEA/NO; 10(-7) M), a spontaneous NO. donor, increased +dP/dt (5 +/- 2%, P < 0.05, n = 6) without augmenting cGMP. SIN-1 and DEA/NO +dP/dt increase persisted despite guanylyl cyclase inhibition with 1H-(1,2,4)oxadiazolo-(4,3,-a)quinoxalin-1-one (10(-5) M, P < 0.05 for both donors), suggesting a cGMP-independent mechanism. Glutathione (5 x 10(-4) M, n = 15) prevented SIN-1 cardiostimulation, suggesting S-NO formation. SIN-1 also produced SOD-inhibitable cardiostimulation in vivo in mice. Thus peroxynitrite and NO donors can stimulate myocardial contractility independently of guanylyl cyclase activation, suggesting a role for S-NO reactions in NO/peroxynitrite-positive inotropic effects in intact hearts. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1117160
- author
- Paolocci, N
; Ekelund, Ulf
LU
; Isoda, T
; Ozaki, M
; Vandegaer, K
; Georgakopoulos, D
; Harrison, R W
; Kass, D A
and Hare, J M
- publishing date
- 2000
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 3-morpholinosydnonimine, myocardial contractility, cyclic nucleotides, superoxide dismutase, glutathione, 1H-(1, 4) oxadiazolo-(4, 2, 3, -a)quinoxalin-1-one, guanosine 3', 5'-cyclic monophosphate
- in
- American Journal of Physiology: Heart and Circulatory Physiology
- volume
- 279
- issue
- 4
- pages
- 1982 - 1988
- publisher
- American Physiological Society
- external identifiers
-
- pmid:11009488
- scopus:0033713239
- ISSN
- 1522-1539
- language
- English
- LU publication?
- no
- id
- 1531a8b0-c61f-4270-9c5d-0422355bb1d1 (old id 1117160)
- alternative location
- http://ajpheart.physiology.org/cgi/content/full/279/4/H1982
- date added to LUP
- 2016-04-01 11:34:13
- date last changed
- 2022-02-03 01:28:17
@article{1531a8b0-c61f-4270-9c5d-0422355bb1d1,
abstract = {{Nitric oxide (NO) has concentration-dependent biphasic myocardial contractile effects. We tested the hypothesis, in isolated rat hearts, that NO cardiostimulation is primarily non-cGMP dependent. Infusion of 3-morpholinosydnonimine (SIN-1, 10(-5) M), which may participate in S-nitrosylation (S-NO) via peroxynitrite formation, increased the rate of left ventricular pressure rise (+dP/dt; 19 +/- 4%, P < 0.001, n = 11) without increasing effluent cGMP or cAMP. Superoxide dismutase (SOD; 150 U/ml) blocked SIN-1 cardiostimulation and led to cGMP elaboration. Sodium nitroprusside (10(-10)-10(-7) M), an iron nitrosyl compound, did not augment +dP/dt but increased cGMP approximately eightfold (P < 0.001), whereas diethylamine/NO (DEA/NO; 10(-7) M), a spontaneous NO. donor, increased +dP/dt (5 +/- 2%, P < 0.05, n = 6) without augmenting cGMP. SIN-1 and DEA/NO +dP/dt increase persisted despite guanylyl cyclase inhibition with 1H-(1,2,4)oxadiazolo-(4,3,-a)quinoxalin-1-one (10(-5) M, P < 0.05 for both donors), suggesting a cGMP-independent mechanism. Glutathione (5 x 10(-4) M, n = 15) prevented SIN-1 cardiostimulation, suggesting S-NO formation. SIN-1 also produced SOD-inhibitable cardiostimulation in vivo in mice. Thus peroxynitrite and NO donors can stimulate myocardial contractility independently of guanylyl cyclase activation, suggesting a role for S-NO reactions in NO/peroxynitrite-positive inotropic effects in intact hearts.}},
author = {{Paolocci, N and Ekelund, Ulf and Isoda, T and Ozaki, M and Vandegaer, K and Georgakopoulos, D and Harrison, R W and Kass, D A and Hare, J M}},
issn = {{1522-1539}},
keywords = {{3-morpholinosydnonimine; myocardial contractility; cyclic nucleotides; superoxide dismutase; glutathione; 1H-(1; 4) oxadiazolo-(4; 2; 3; -a)quinoxalin-1-one; guanosine 3'; 5'-cyclic monophosphate}},
language = {{eng}},
number = {{4}},
pages = {{1982--1988}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology: Heart and Circulatory Physiology}},
title = {{cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation}},
url = {{http://ajpheart.physiology.org/cgi/content/full/279/4/H1982}},
volume = {{279}},
year = {{2000}},
}