Cyclic GMP decreases cardiac myocyte oxygen consumption to a greater extent under conditions of increased metabolism

Gary X. Gong, Harvey R. Weiss, James Tse, Peter M. Scholz

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

We tested the hypothesis that the negative effects of intracellular guanosine 3',5'-cyclic monophosphate (cyclic GMP) were more profound on cardiac myocyte oxygen consumption (VO2) during increased metabolism of the myocytes. The steady state VO2 of a suspension of single myocytes isolated from hearts of New Zealand White rabbits was measured in a glass chamber by using a Clark-type oxygen electrode, and cyclic GMP was determined by using a radioimmunoassay. The cellular cyclic GMP levels were increased either by adding 3-morpholino-sydnonimine (SIN-I), a guanylate cyciasa stimulator, or zaprinast (ZAP), a cyclic GMP-phosphodiesterase inhibitor, at various doses. In 0.5 mM Ca2+ medium, average Vo2 was 123 ± 8 hi/rain/100,000 cells, and cyclic GMP was 3.4 ± 9.3 fmol/100,000 cells, and these increased significantly to 182 ± 9 nl/min/100,000 cells and 78.2 ± 7.3 fmol/100,000 cells in 2.0 mM Ca2+. There were dose-depeudent responses of the VO2 and cellular cyclic GMP levels in responding to both SIN-I and ZAR. An inverse relation between cellular cyclic GMP level and Vo2 existed in the myocytes. The regression equations for the four treatments were Iog(Vo2) = - 0.002[cyclic GMP] + 2.19, r = 0.96 for SIN-1 in low (0.5 mM) Ca2+; log(VO2) = 0.005[cyclic GMP] + 1.80, r = 0.38 for ZAP in low Ca2+; 1og(VO2) = -0.001[cyclic GMP] + 2.24, r = 0.82 for SIN-I in high (2.0 mM) Ca2+; and log(VO2) = -0.004[cyclic GMP] + 2.56, r = 0.93 for ZAP in high Ca2+. The slope of ZAP regression line was significantly more negative than that of SIN-1 with high calcium. At any given level of cyclic GMP, ZAP decreased the VO2 to a greater extent than did SIN-1 although the latter caused the maximal increase in cyclic GMP level. The reduction in VO2 caused by a corresponding increase in cellular cyclic GMP was greater in myocytes incubated with high-Ca2+ medium.

Original languageEnglish (US)
Pages (from-to)537-543
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume30
Issue number4
DOIs
StatePublished - Dec 29 1997

Fingerprint

Cyclic GMP
Cardiac Myocytes
Oxygen Consumption
Muscle Cells
Phosphodiesterase Inhibitors
Rain
Radioimmunoassay
Glass
Suspensions

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Keywords

  • Calcium
  • Cardiac myocytes
  • Cycllc GMP
  • Oxygen consumption
  • Rabbit

Cite this

@article{adea49864c0f43feada64795ad49eb72,
title = "Cyclic GMP decreases cardiac myocyte oxygen consumption to a greater extent under conditions of increased metabolism",
abstract = "We tested the hypothesis that the negative effects of intracellular guanosine 3',5'-cyclic monophosphate (cyclic GMP) were more profound on cardiac myocyte oxygen consumption (VO2) during increased metabolism of the myocytes. The steady state VO2 of a suspension of single myocytes isolated from hearts of New Zealand White rabbits was measured in a glass chamber by using a Clark-type oxygen electrode, and cyclic GMP was determined by using a radioimmunoassay. The cellular cyclic GMP levels were increased either by adding 3-morpholino-sydnonimine (SIN-I), a guanylate cyciasa stimulator, or zaprinast (ZAP), a cyclic GMP-phosphodiesterase inhibitor, at various doses. In 0.5 mM Ca2+ medium, average Vo2 was 123 ± 8 hi/rain/100,000 cells, and cyclic GMP was 3.4 ± 9.3 fmol/100,000 cells, and these increased significantly to 182 ± 9 nl/min/100,000 cells and 78.2 ± 7.3 fmol/100,000 cells in 2.0 mM Ca2+. There were dose-depeudent responses of the VO2 and cellular cyclic GMP levels in responding to both SIN-I and ZAR. An inverse relation between cellular cyclic GMP level and Vo2 existed in the myocytes. The regression equations for the four treatments were Iog(Vo2) = - 0.002[cyclic GMP] + 2.19, r = 0.96 for SIN-1 in low (0.5 mM) Ca2+; log(VO2) = 0.005[cyclic GMP] + 1.80, r = 0.38 for ZAP in low Ca2+; 1og(VO2) = -0.001[cyclic GMP] + 2.24, r = 0.82 for SIN-I in high (2.0 mM) Ca2+; and log(VO2) = -0.004[cyclic GMP] + 2.56, r = 0.93 for ZAP in high Ca2+. The slope of ZAP regression line was significantly more negative than that of SIN-1 with high calcium. At any given level of cyclic GMP, ZAP decreased the VO2 to a greater extent than did SIN-1 although the latter caused the maximal increase in cyclic GMP level. The reduction in VO2 caused by a corresponding increase in cellular cyclic GMP was greater in myocytes incubated with high-Ca2+ medium.",
keywords = "Calcium, Cardiac myocytes, Cycllc GMP, Oxygen consumption, Rabbit",
author = "Gong, {Gary X.} and Weiss, {Harvey R.} and James Tse and Scholz, {Peter M.}",
year = "1997",
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Cyclic GMP decreases cardiac myocyte oxygen consumption to a greater extent under conditions of increased metabolism. / Gong, Gary X.; Weiss, Harvey R.; Tse, James; Scholz, Peter M.

In: Journal of Cardiovascular Pharmacology, Vol. 30, No. 4, 29.12.1997, p. 537-543.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cyclic GMP decreases cardiac myocyte oxygen consumption to a greater extent under conditions of increased metabolism

AU - Gong, Gary X.

AU - Weiss, Harvey R.

AU - Tse, James

AU - Scholz, Peter M.

PY - 1997/12/29

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N2 - We tested the hypothesis that the negative effects of intracellular guanosine 3',5'-cyclic monophosphate (cyclic GMP) were more profound on cardiac myocyte oxygen consumption (VO2) during increased metabolism of the myocytes. The steady state VO2 of a suspension of single myocytes isolated from hearts of New Zealand White rabbits was measured in a glass chamber by using a Clark-type oxygen electrode, and cyclic GMP was determined by using a radioimmunoassay. The cellular cyclic GMP levels were increased either by adding 3-morpholino-sydnonimine (SIN-I), a guanylate cyciasa stimulator, or zaprinast (ZAP), a cyclic GMP-phosphodiesterase inhibitor, at various doses. In 0.5 mM Ca2+ medium, average Vo2 was 123 ± 8 hi/rain/100,000 cells, and cyclic GMP was 3.4 ± 9.3 fmol/100,000 cells, and these increased significantly to 182 ± 9 nl/min/100,000 cells and 78.2 ± 7.3 fmol/100,000 cells in 2.0 mM Ca2+. There were dose-depeudent responses of the VO2 and cellular cyclic GMP levels in responding to both SIN-I and ZAR. An inverse relation between cellular cyclic GMP level and Vo2 existed in the myocytes. The regression equations for the four treatments were Iog(Vo2) = - 0.002[cyclic GMP] + 2.19, r = 0.96 for SIN-1 in low (0.5 mM) Ca2+; log(VO2) = 0.005[cyclic GMP] + 1.80, r = 0.38 for ZAP in low Ca2+; 1og(VO2) = -0.001[cyclic GMP] + 2.24, r = 0.82 for SIN-I in high (2.0 mM) Ca2+; and log(VO2) = -0.004[cyclic GMP] + 2.56, r = 0.93 for ZAP in high Ca2+. The slope of ZAP regression line was significantly more negative than that of SIN-1 with high calcium. At any given level of cyclic GMP, ZAP decreased the VO2 to a greater extent than did SIN-1 although the latter caused the maximal increase in cyclic GMP level. The reduction in VO2 caused by a corresponding increase in cellular cyclic GMP was greater in myocytes incubated with high-Ca2+ medium.

AB - We tested the hypothesis that the negative effects of intracellular guanosine 3',5'-cyclic monophosphate (cyclic GMP) were more profound on cardiac myocyte oxygen consumption (VO2) during increased metabolism of the myocytes. The steady state VO2 of a suspension of single myocytes isolated from hearts of New Zealand White rabbits was measured in a glass chamber by using a Clark-type oxygen electrode, and cyclic GMP was determined by using a radioimmunoassay. The cellular cyclic GMP levels were increased either by adding 3-morpholino-sydnonimine (SIN-I), a guanylate cyciasa stimulator, or zaprinast (ZAP), a cyclic GMP-phosphodiesterase inhibitor, at various doses. In 0.5 mM Ca2+ medium, average Vo2 was 123 ± 8 hi/rain/100,000 cells, and cyclic GMP was 3.4 ± 9.3 fmol/100,000 cells, and these increased significantly to 182 ± 9 nl/min/100,000 cells and 78.2 ± 7.3 fmol/100,000 cells in 2.0 mM Ca2+. There were dose-depeudent responses of the VO2 and cellular cyclic GMP levels in responding to both SIN-I and ZAR. An inverse relation between cellular cyclic GMP level and Vo2 existed in the myocytes. The regression equations for the four treatments were Iog(Vo2) = - 0.002[cyclic GMP] + 2.19, r = 0.96 for SIN-1 in low (0.5 mM) Ca2+; log(VO2) = 0.005[cyclic GMP] + 1.80, r = 0.38 for ZAP in low Ca2+; 1og(VO2) = -0.001[cyclic GMP] + 2.24, r = 0.82 for SIN-I in high (2.0 mM) Ca2+; and log(VO2) = -0.004[cyclic GMP] + 2.56, r = 0.93 for ZAP in high Ca2+. The slope of ZAP regression line was significantly more negative than that of SIN-1 with high calcium. At any given level of cyclic GMP, ZAP decreased the VO2 to a greater extent than did SIN-1 although the latter caused the maximal increase in cyclic GMP level. The reduction in VO2 caused by a corresponding increase in cellular cyclic GMP was greater in myocytes incubated with high-Ca2+ medium.

KW - Calcium

KW - Cardiac myocytes

KW - Cycllc GMP

KW - Oxygen consumption

KW - Rabbit

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