ALTERED RELATIONSHIP BETWEEN CYCLIC-GMP AND MYOCARDIAL O-2 CONSUMPTION IN RENAL HYPERTENSION-INDUCED CARDIAC-HYPERTROPHY

Citation
P. Rabindranauth et al., ALTERED RELATIONSHIP BETWEEN CYCLIC-GMP AND MYOCARDIAL O-2 CONSUMPTION IN RENAL HYPERTENSION-INDUCED CARDIAC-HYPERTROPHY, Research in experimental medicine, 198(1), 1998, pp. 11-21
Citations number
33
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
03009130
Volume
198
Issue
1
Year of publication
1998
Pages
11 - 21
Database
ISI
SICI code
0300-9130(1998)198:1<11:ARBCAM>2.0.ZU;2-U
Abstract
We tested the hypothesis that preventing cyclic GMP degradation with z aprinast, (a selective cyclic GMP-phosphodiesterase inhibitor) would p roduce a blunted reduction in myocardial O-2 consumption in renal hype rtension (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 (3x10(-3) M) was applied to pically to the left ventricular surface of control or 1K1C rabbits. Co ronary blood flow (radioactive microspheres) and O-2 extraction (micro spectrophotometry) were used to determine O-2 consumption. Myocardial cyclic GMP levels were determined by radioimmunoassay. The 1K1C rabbit s 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 signific antly and similarly increased cyclic GMP in both control (3.90 +/- 0.4 7 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 O-2 consumption (ml O-2/min/100 g) was significantly lower in control s 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 (E PI: 10.3 +/- 2.4; ENDO: 11.2 +/- 2.6) compared with the vehicle-treate d 1K1C group (EPI: 13.3 +/- 1.2, ENDO: 14.5 +/- 2.4). There was a simi lar increase in myocardial cyclic GMP after treatment with zaprinast, but a greater depression of myocardial O-2 consumption in control anim als than in 1K1C after treatment with zaprinast. This suggested that t he reduction in myocardial O-2 consumption, related to increases in cy clic GMP caused by cyclic GMP-phosphodiesterase blockade, was less in 1K1C cardiac hypertrophy.