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
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.