L-arginjne in the development and reversal of tolerance to nitroglycerin

G. Abou-Molmmed, A. Suarez, W. H. Kaesemever, A. Panapetroooulos, J. D. Catravas, Robert William Caldwell

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Nitroglyeerin (GTN) and sodium nitroprusside (SNP) have different vasodilator profiles and tolerance is evident clinically only with GTN. Our purpose was to determine mechanistic differences between these two agents and any relationship of differences to the development of tolerance. Tolerance to the relaxation of rat aortic rings to GTN was evident after 2 hours of exposure to GTN followed by a 1 hr drug-free interval. The ability of L-arginine to reverse tolerance to GTN was determined. Tissue content of L-arginine was assayed before and after exposure to GTN for 2 hours. Concentration-relaxation curves were constructed for GTN with and without L-arginine. cGMP production was measured in aortic rings. Tolerance developed in aorta incubated with GTN as evident by a 71 fold rightward shift of the dose response curve. This shift was associated with a 40% reduction in L-arginine tissue levels. Adding L-arginine to aortic tissue was associated with a significant reduction in rightward shift (9 x fold). Addition of GTN to stimulate production of cGMP revealed that L-arginine potentiated the action of GTN. In summary, L-arjjnine reverses tolerance to GTN in isolated vascular tissues. The actions of GTN are dependent on Larginine which decreases in tissues at the point of development of tolerance to GTN. The mechanism by which GTN depletes L-arginine is being investigated.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

Fingerprint

Nitroglycerin
arginine
Arginine
Tissue
vasodilator agents
vascular tissues
Nitroprusside
aorta
nitroglycerin
Vasodilator Agents
dose response
Blood Vessels
Aorta
Rats
drugs
tissues
rats
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Abou-Molmmed, G., Suarez, A., Kaesemever, W. H., Panapetroooulos, A., Catravas, J. D., & Caldwell, R. W. (1996). L-arginjne in the development and reversal of tolerance to nitroglycerin. FASEB Journal, 10(3).

L-arginjne in the development and reversal of tolerance to nitroglycerin. / Abou-Molmmed, G.; Suarez, A.; Kaesemever, W. H.; Panapetroooulos, A.; Catravas, J. D.; Caldwell, Robert William.

In: FASEB Journal, Vol. 10, No. 3, 01.12.1996.

Research output: Contribution to journalArticle

Abou-Molmmed, G, Suarez, A, Kaesemever, WH, Panapetroooulos, A, Catravas, JD & Caldwell, RW 1996, 'L-arginjne in the development and reversal of tolerance to nitroglycerin', FASEB Journal, vol. 10, no. 3.
Abou-Molmmed G, Suarez A, Kaesemever WH, Panapetroooulos A, Catravas JD, Caldwell RW. L-arginjne in the development and reversal of tolerance to nitroglycerin. FASEB Journal. 1996 Dec 1;10(3).
Abou-Molmmed, G. ; Suarez, A. ; Kaesemever, W. H. ; Panapetroooulos, A. ; Catravas, J. D. ; Caldwell, Robert William. / L-arginjne in the development and reversal of tolerance to nitroglycerin. In: FASEB Journal. 1996 ; Vol. 10, No. 3.
@article{87bcb37a2e8043fda83c632aa8dff23a,
title = "L-arginjne in the development and reversal of tolerance to nitroglycerin",
abstract = "Nitroglyeerin (GTN) and sodium nitroprusside (SNP) have different vasodilator profiles and tolerance is evident clinically only with GTN. Our purpose was to determine mechanistic differences between these two agents and any relationship of differences to the development of tolerance. Tolerance to the relaxation of rat aortic rings to GTN was evident after 2 hours of exposure to GTN followed by a 1 hr drug-free interval. The ability of L-arginine to reverse tolerance to GTN was determined. Tissue content of L-arginine was assayed before and after exposure to GTN for 2 hours. Concentration-relaxation curves were constructed for GTN with and without L-arginine. cGMP production was measured in aortic rings. Tolerance developed in aorta incubated with GTN as evident by a 71 fold rightward shift of the dose response curve. This shift was associated with a 40{\%} reduction in L-arginine tissue levels. Adding L-arginine to aortic tissue was associated with a significant reduction in rightward shift (9 x fold). Addition of GTN to stimulate production of cGMP revealed that L-arginine potentiated the action of GTN. In summary, L-arjjnine reverses tolerance to GTN in isolated vascular tissues. The actions of GTN are dependent on Larginine which decreases in tissues at the point of development of tolerance to GTN. The mechanism by which GTN depletes L-arginine is being investigated.",
author = "G. Abou-Molmmed and A. Suarez and Kaesemever, {W. H.} and A. Panapetroooulos and Catravas, {J. D.} and Caldwell, {Robert William}",
year = "1996",
month = "12",
day = "1",
language = "English (US)",
volume = "10",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "3",

}

TY - JOUR

T1 - L-arginjne in the development and reversal of tolerance to nitroglycerin

AU - Abou-Molmmed, G.

AU - Suarez, A.

AU - Kaesemever, W. H.

AU - Panapetroooulos, A.

AU - Catravas, J. D.

AU - Caldwell, Robert William

PY - 1996/12/1

Y1 - 1996/12/1

N2 - Nitroglyeerin (GTN) and sodium nitroprusside (SNP) have different vasodilator profiles and tolerance is evident clinically only with GTN. Our purpose was to determine mechanistic differences between these two agents and any relationship of differences to the development of tolerance. Tolerance to the relaxation of rat aortic rings to GTN was evident after 2 hours of exposure to GTN followed by a 1 hr drug-free interval. The ability of L-arginine to reverse tolerance to GTN was determined. Tissue content of L-arginine was assayed before and after exposure to GTN for 2 hours. Concentration-relaxation curves were constructed for GTN with and without L-arginine. cGMP production was measured in aortic rings. Tolerance developed in aorta incubated with GTN as evident by a 71 fold rightward shift of the dose response curve. This shift was associated with a 40% reduction in L-arginine tissue levels. Adding L-arginine to aortic tissue was associated with a significant reduction in rightward shift (9 x fold). Addition of GTN to stimulate production of cGMP revealed that L-arginine potentiated the action of GTN. In summary, L-arjjnine reverses tolerance to GTN in isolated vascular tissues. The actions of GTN are dependent on Larginine which decreases in tissues at the point of development of tolerance to GTN. The mechanism by which GTN depletes L-arginine is being investigated.

AB - Nitroglyeerin (GTN) and sodium nitroprusside (SNP) have different vasodilator profiles and tolerance is evident clinically only with GTN. Our purpose was to determine mechanistic differences between these two agents and any relationship of differences to the development of tolerance. Tolerance to the relaxation of rat aortic rings to GTN was evident after 2 hours of exposure to GTN followed by a 1 hr drug-free interval. The ability of L-arginine to reverse tolerance to GTN was determined. Tissue content of L-arginine was assayed before and after exposure to GTN for 2 hours. Concentration-relaxation curves were constructed for GTN with and without L-arginine. cGMP production was measured in aortic rings. Tolerance developed in aorta incubated with GTN as evident by a 71 fold rightward shift of the dose response curve. This shift was associated with a 40% reduction in L-arginine tissue levels. Adding L-arginine to aortic tissue was associated with a significant reduction in rightward shift (9 x fold). Addition of GTN to stimulate production of cGMP revealed that L-arginine potentiated the action of GTN. In summary, L-arjjnine reverses tolerance to GTN in isolated vascular tissues. The actions of GTN are dependent on Larginine which decreases in tissues at the point of development of tolerance to GTN. The mechanism by which GTN depletes L-arginine is being investigated.

UR - http://www.scopus.com/inward/record.url?scp=4243567977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4243567977&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:4243567977

VL - 10

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 3

ER -