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Negative Functional Effects of Natriuretic Peptides Are Attenuated in Hypertrophic Cardiac Myocytes by Reduced Particulate Guanylyl Cyclase Activity
- Source :
- Journal of Cardiovascular Pharmacology. 49:100-105
- Publication Year :
- 2007
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2007.
-
Abstract
- We tested the hypothesis that the negative functional effects of natriuretic peptides would be blunted in thyroxine (T4)-induced hypertrophic cardiac myocytes. We also studied the causes of these changes. Ventricular myocytes were obtained from control (n=8) and T4 (0.5 mg/kg/16 days) treated rabbit hearts (n=7). Cell shortening parameters were studied with a video edge detector. We also determined particulate (pGC) and soluble (sGC) guanylyl cyclase activity and cyclic GMP levels. Myocyte function was examined at baseline and after brain natriuretic peptide (BNP 10(-7,-6) M) or C-type natriuretic peptide (CNP 10(-7,-6) M) or zaprinast (cyclic GMP phosphodiesterase inhibitor 10(-6)M) followed by BNP or CNP. Baseline function was similar in control and T4 myocytes. BNP (5.7 +/- 0.2 to 4.3 +/- 0.1%) and CNP (5.7 +/- 0.4 to 4.2 +/- 0.2%) significantly reduced percent shortening in control myocytes. These reductions were not observed with T4 (BNP, 5.7 +/- 0.6 to 5.6 +/- 0.6; CNP, 5.6 +/- 0.4 to 5.5 +/- 0.5). BNP and CNP responded similarly after zaprinast. Baseline cyclic GMP was similar in control and T4, but BNP only increased cyclic GMP in controls. The activity of pGC was similar at baseline in control and T4, but the stimulated activity was significantly lower in T4 myocytes. Both basal and stimulated sGC activity were similar in control and hypertrophic myocytes. These results demonstrated that the ability of natriuretic peptides to reduce ventricular myocyte function was blunted in T4 hypertrophic myocytes. This blunted response was related to the reduced ability of natriuretic peptides to increase cyclic GMP levels due to a reduced stimulated particulate guanylyl cyclase activity.
- Subjects :
- medicine.medical_specialty
Edge detector
Purinones
Phosphodiesterase Inhibitors
medicine.drug_class
Guanylyl cyclase activity
In Vitro Techniques
Basal (phylogenetics)
Cyclic gmp
chemistry.chemical_compound
3',5'-Cyclic-GMP Phosphodiesterases
Internal medicine
Natriuretic Peptide, Brain
medicine
Natriuretic peptide
Animals
Myocyte
Myocytes, Cardiac
Natriuretic Peptides
Cyclic GMP
Cell Size
Pharmacology
Chemistry
Natriuretic Peptide, C-Type
Brain natriuretic peptide
Thyroxine
Endocrinology
Guanylate Cyclase
cardiovascular system
Rabbits
Cardiology and Cardiovascular Medicine
Zaprinast
Subjects
Details
- ISSN :
- 01602446
- Volume :
- 49
- Database :
- OpenAIRE
- Journal :
- Journal of Cardiovascular Pharmacology
- Accession number :
- edsair.doi.dedup.....2bf6e8226f2a1a41bbc70c56855d4629