| Altered relationship between cyclic GMP and myocardial O2 consumption in renal hypertension-induced cardiac hypertrophy. | |
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MedLine Citation:
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PMID: 9706666 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We tested the hypothesis that preventing cyclic GMP degradation with zaprinast, (a selective cyclic GMP-phosphodiesterase inhibitor) would produce a blunted reduction in myocardial O2 consumption in renal hypertension (One Kidney-One Clip, 1K1C)-induced cardiac hypertrophy. Four groups of anesthetized open-chest New Zealand white rabbits (n = 26) were utilized. Either vehicle or zaprinast (3 x 10(-3) M) was applied topically to the left ventricular surface of control or 1K1C rabbits. Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to determine O2 consumption. Myocardial cyclic GMP levels were determined by radioimmunoassay. The 1K1C rabbits had a greater heart weight-to-body weight ratio (2.94 +/- 0.08 g/kg) than controls (2.58 +/- 0.17). Systolic blood pressure was higher in 1K1C (102 +/- 9 mm Hg) than in controls (86 +/- 3). Zaprinast significantly and similarly increased cyclic GMP in both control (3.90 +/- 0.47 to 4.66 +/- 0.89 pmol/g) subepicardium (EPI) and (5.08 +/- 0.69 to 7.06 +/- 1.36) subendocardium (ENDO) and 1K1C hearts (5.53 +/- 0.61 to 7.48 +/- 1.51 EPI and 6.48 +/- 0.42 to 8.88 +/- 1.08 ENDO). Myocardial O2 consumption (ml O2/min/ 100 g) was significantly lower in controls treated with zaprinast (EPI: 8.8 +/- 0.1; ENDO: 9.5 +/- 1.9) than in controls treated with vehicle (EPI: 13.6 +/- 1.3; ENDO: 16.2 +/- 2.9). This effect was diminished in 1K1C rabbits treated with zaprinast (EPI: 10.3 +/- 2.4; ENDO: 11.2 +/- 2.6) compared with the vehicle-treated 1K1C group (EPI: 13.3 +/- 1.2; ENDO: 14.5 +/- 2.4). There was a similar increase in myocardial cyclic GMP after treatment with zaprinast, but a greater depression of myocardial O2 consumption in control animals than in 1K1C after treatment with zaprinast. This suggested that the reduction in myocardial O2 consumption, related to increases in cyclic GMP caused by cyclic GMP-phosphodiesterase blockade, was less in 1K1C cardiac hypertrophy. |
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Authors:
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P Rabindranauth; P M Scholz; J Tse; K L Naim; H R Weiss |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Research in experimental medicine. Zeitschrift für die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie Volume: 198 ISSN: 0300-9130 ISO Abbreviation: Res Exp Med (Berl) Publication Date: 1998 Jul |
Date Detail:
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Created Date: 1998-10-27 Completed Date: 1998-10-27 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0324736 Medline TA: Res Exp Med (Berl) Country: GERMANY |
Other Details:
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Languages: eng Pagination: 11-21 Citation Subset: IM |
Affiliation:
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Department of Physiology & Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Cardiomegaly / etiology, metabolism* Coronary Circulation / drug effects Cyclic GMP / analysis, metabolism* Hemodynamics Hypertension, Renovascular / complications Microspheres Myocardium / metabolism* Oxygen Consumption* Phosphodiesterase Inhibitors / pharmacology* Purinones / pharmacology* Rabbits |
| Grant Support | |
ID/Acronym/Agency:
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HL40320/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Phosphodiesterase Inhibitors; 0/Purinones; 37762-06-4/zaprinast; 7665-99-8/Cyclic GMP |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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