| Decreasing cyclic GMP exerts similar positive functional effects on cardiac myocytes regardless of initial level. | |
| | |
MedLine Citation:
|
PMID: 10895081 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
We tested the hypothesis that lowering the level of cyclic GMP would have positive functional effects on isolated rabbit ventricular myocytes regardless of the basal cyclic GMP level. Cell shortening data were collected with a video detector; O(2) consumption data were obtained with a Clark electrode; intracellular cyclic GMP levels were obtained by radioimmunoassay. Data were obtained: (1) at baseline; (2) after the addition of 1H-[1,2,4]oxadiazolo[4, 3-alpha]quinoxaline-1-one (ODQ) 10(-6) and 10(-4) mol/l, a selective soluble guanylyl cyclase inhibitor, and (3) after zaprinast 10(-6) mol/l, a cyclic GMP phosphodiesterase inhibitor, followed by ODQ 10(-6) and 10(-4) mol/l. We found that ODQ 10(-4) mol/l significantly decreased the cyclic GMP level from 493 +/- 75 to 301 +/- 78 (fmol/100,000 myocytes) and increased percent shortening (Pcs, %; 4.9 +/- 0.3 vs. 5.8 +/- 0.6) and maximum rate of shortening (Rs, microm/s; 58.7 +/- 5.7 vs. 73.6 +/- 4.9). Zaprinast significantly increased the cyclic GMP level from 419 +/- 140 to 599 +/- 241 and decreased Pcs (6.2 +/- 0.5 vs. 4.4 +/- 0.4) and Rs (65.5 +/- 5.3 vs. 49.6 +/- 4.3). After zaprinast, ODQ 10(-4) mol/l decreased the cyclic GMP level to 439 +/- 139 and increased percent shortening and rate of shortening by a similar percentage compared to the non-zaprinast treated myocytes. We conclude that in rabbit ventricular myocytes, a reduction in the level of myocyte cyclic GMP increases myocyte function independent of the initial cyclic GMP level. |
| | |
Authors:
|
L Yan; M W Huang; P M Scholz; H R Weiss |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Pharmacology Volume: 61 ISSN: 0031-7012 ISO Abbreviation: Pharmacology Publication Date: 2000 Jul |
Date Detail:
|
Created Date: 2000-08-24 Completed Date: 2000-08-24 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 0152016 Medline TA: Pharmacology Country: SWITZERLAND |
Other Details:
|
Languages: eng Pagination: 51-6 Citation Subset: IM |
Copyright Information:
|
Copyright 2000 S. Karger AG, Basel |
Affiliation:
|
Heart and Brain Circulation Laboratory, Departments of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cyclic GMP / analysis, physiology* Guanylate Cyclase / metabolism Heart / physiology* Myocardium / cytology, metabolism Oxadiazoles / pharmacology Oxygen Consumption / drug effects Purinones / pharmacology Quinoxalines / pharmacology Rabbits |
| Grant Support | |
ID/Acronym/Agency:
|
HL-40320/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/Oxadiazoles; 0/Purinones; 0/Quinoxalines; 37762-06-4/zaprinast; 7665-99-8/Cyclic GMP; EC 4.6.1.2/Guanylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: On the cardiac contractile, electrophysiological and biochemical effects of endothall, a protein pho...
Next Document: Ureterointestinal anastomosis in orthotopic neobladders.