What question did this study set out to answer?

To determine whether cyclic GMP protein kinase mediates the depressive metabolic and functional effects of cyclic GMP in healthy and hypertrophied rabbit cardiac myocytes.

August 1, 1999Journal of Cardiovascular Pharmacology

Cyclic GMP Protein Kinase Mediates Negative Metabolic and Functional Effects of Cyclic GMP in Control and Hypertrophied Rabbit Cardiac Myocytes

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Why the study?

Does cyclic GMP protein kinase inhibition alter the negative metabolic and functional effects of increased cyclic GMP in control and hypertrophied rabbit cardiac myocytes?

Population

Isolated cardiac myocytes from control and renal hypertensive cardiac hypertrophic rabbits

Comparison

Cyclic GMP protein kinase inhibitors KT5823 (10… vs Baseline conditions or zaprinast alone

Design

Preclinical

Authors

MSMichaela StraznickaRutgers, The State University of New Jersey GGGary GongUConn Health LYLin YanMerck & Co., Inc., Rahway, NJ, USA (United States)

Discussion

Member takes

Implication

PKG inhibition may offset cGMP effects in hypertrophied myocytes; leaves open translation to human HF therapy.

Key Points

To determine whether cyclic GMP protein kinase mediates the depressive metabolic and functional effects of cyclic GMP in healthy and hypertrophied rabbit cardiac myocytes.
Isolated cardiac myocytes from healthy control rabbits and one-kidney, one-clip (1K1C) renal hypertensive hypertrophic rabbits.
Measured myocyte oxygen consumption, cyclic GMP accumulation, and percentage cell shortening at baseline and following exposure to zaprinast with or without protein kinase inhibitors (KT5823 or Rp-8-pCPT-cGMP).
Basal cyclic GMP concentrations were 62 ± 10 pmol/10^5 myocytes in controls versus 66 ± 17 pmol/10^5 myocytes in 1K1C cells, with zaprinast inducing dose-dependent cyclic GMP increases in both groups.
Zaprinast significantly and dose-dependently reduced myocyte oxygen consumption and percentage cell shortening, both of which were partially restored by KT5823.
Kinase inhibitors KT5823 and Rp-8-pCPT-cGMP had no functional or metabolic effect under basal conditions, demonstrating equivalent efficacy only when cyclic GMP was elevated in control and hypertrophic cells.

Structured PICO

Does cyclic GMP protein kinase inhibition alter the negative metabolic and functional effects of increased cyclic GMP in control and hypertrophied rabbit cardiac myocytes?

Population

Isolated cardiac myocytes from control and renal hypertensive (one-kidney, one-clip, 1K1C) cardiac hypertrophic rabbits

Intervention

Cyclic GMP protein kinase inhibitors KT5823 (10(-6) M) or Rp8-pCPT-cGMP (5 x 10(-6) M) with or without cyclic GMP phosphodiesterase inhibitor zaprinast (10(-6), 10(-4) M)

Comparator

Baseline conditions or zaprinast alone

Outcome

Oxygen consumption (Mvo2), cyclic GMP levels, and cell shorteningsurrogate

Cyclic GMP protein kinase mediates the negative metabolic and functional effects of increased intracellular cyclic GMP in both normal and hypertrophied rabbit cardiac myocytes.

Cite This Study

Straznicka et al. (1999) studied this question.

synapsesocial.com/papers/6a78c3c62e130d02afed4d78 https://doi.org/10.1097/00005344-199908000-00008

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Cyclic GMP Protein Kinase Mediates Negative Metabolic and Functional Effects of Cyclic GMP in Control and Hypertrophied Rabbit Cardiac Myocytes

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Cyclic GMP Protein Kinase Mediates Negative Metabolic and Functional Effects of Cyclic GMP in Control and Hypertrophied Rabbit Cardiac Myocytes

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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