Milrinone, a cyclic AMP-phosphodiesterase inhibitor, has differential effects on regional myocardial work and oxygen consumption in experimental left ventricular hypertrophy

1994 ◽  
Vol 28 (9) ◽  
pp. 1360-1365 ◽  
Author(s):  
W. C Chiu ◽  
J. Kedem ◽  
H. R Weiss ◽  
J. Tse ◽  
B. V Cheinberg ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Cyclic Amp ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Phosphodiesterase Inhibitor ◽  
Left Ventricular ◽  
Differential Effects ◽  
Cyclic Amp Phosphodiesterase

scholarly journals 2 Differential effects of left ventricular hypertrophy on coronary haemodynamics in aortic stenosis and hypertension

2021 ◽  
Author(s):  
Anenta Ramakrishnan ◽  
Nearchos Hadjiloizou ◽  
Yousif Ahmad ◽  
Sayan Sen ◽  
Iqbal Malik ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Aortic Stenosis ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Differential Effects

Cyclic GMP and cyclic AMP induced changes in control and hypertrophic cardiac myocyte function interact through cyclic GMP affected cyclic-AMP phosphodiesterases

1999 ◽  
Vol 77 (6) ◽  
pp. 422-431 ◽  
Author(s):  
Harvey R Weiss ◽  
Gary X Gong ◽  
Michaela Straznicka ◽  
Lin Yan ◽  
James Tse ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Left Ventricular Hypertrophy ◽  
Cyclic Gmp ◽  
Ventricular Hypertrophy ◽  
Cardiac Myocyte ◽  
Second Messengers ◽  
Left Ventricular ◽  
Competitive Binding Assay ◽  
Myocyte Function ◽  
Camp Levels

We tested the hypothesis that the negative functional effects of cyclic GMP (cGMP) would be greater after increasing cyclic AMP (cAMP), because of the action of cGMP-affected cAMP phosphodiesterases in cardiac myocytes and that this effect would be altered in left ventricular hypertrophy (LVH) produced by aortic valve plication. Myocyte shortening data were collected using a video edge detector, and O2 consumption was measured by O2 electrodes during stimulation (5 ms, 1 Hz, in 2 mM Ca2+) from control (n = 7) and LVH (n = 7) dog ventricular myocytes. cAMP and cGMP were determined by a competitive binding assay. cAMP was increased by forskolin and milrinone (10-6 M). cGMP was increased with zaprinast and decreased by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxilin-1-one (ODQ) both at 10-6 and 10-4 M, with and without forskolin or forskolin + milrinone. Zaprinast significantly decreased percent shortening in control (9 ± 1 to 7 ± 1%) and LVH (10 ± 1 to 7 ± 1%) myocytes. It increased cGMP in control (36 ± 5 to 52 ± 7 fmol/105 myocytes) and from the significantly higher baseline value in LVH (71 ± 12 to 104 ± 18 fmol/105 myocytes). ODQ increased myocyte function and decreased cGMP levels in control and LVH myocytes. Forskolin + milrinone increased cAMP levels in control (6 ± 1 to 15 ± 2 pmol/105 myocytes) and LVH (8 ± 1 to 18 ± 2 pmol/105 myocytes) myocytes, as did forskolin alone. They also significantly increased percent shortening. There were significant negative functional effects of zaprinast after forskolin + milrinone in control (15 ± 2 to 9 ± 1%), which were greater than zaprinast alone, and LVH (12 ± 1 to 9 ± 1%). This was associated with an increase in cGMP and a reduction in the increased cAMP induced by forskolin or milrinone. ODQ did not further increase function after forskolin or milrinone in control myocytes, despite lowering cGMP. However, it prevented the forskolin and milrinone induced increase in cAMP. In hypertrophy, ODQ lowered cGMP and increased function after forskolin. ODQ did not affect cAMP after forskolin and milrinone in LVH. Thus, the level of cGMP was inversely correlated with myocyte function. When cAMP levels were elevated, cGMP was still inversely correlated with myocyte function. This was, in part, related to alterations in cAMP. The interaction between cGMP and cAMP was altered in LVH myocytes.Key words: second messengers, cyclic AMP, cyclic GMP, cardiac myocyte function, cyclic GMP dependent cyclic-AMP phosphodiesterases, left ventricular hypertrophy, dog.

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