Rj. Leone et al., Cyclic GMP attenuates cyclic AMP-stimulated inotropy and oxygen consumption in control and hypertrophic hearts, BAS R CARD, 95(1), 2000, pp. 28-38
We tested the hypothesis that increasing myocardial cyclic GMP would attenu
ate cyclic AMP induced positive inotropy and O-2 consumption, in part, thro
ugh changes in cyclic AR IP and that renal hypertension-induced cardiac hyp
ertrophy (HYP) would alter this relationship. Anesthetized, open chest rabb
its (N = 48) were divided into four groups of control (CON) and HYP animals
which received vehicle (VEH), isoproterenol 10(-6)M (ISO), 3-morpholinosyn
dnonimine 10(-4)M, (SIN-1), or a combination of ISO+SIN-1. Coronary blood f
low (microspheres) and O-2 extraction (microspectrophotometry) were used to
determine O-2 consumption in both subepicardium (EPI) and subendocardium (
ENDO). Left ventricular change in wall thickness (%) was increased signific
antly by ISO in both CON (16 +/- 4 to 31 +/- 6) and HYP (17 +/- 2 to 24 +/-
3). Percent change in wall thickness was similar in the CON, SIN-1, and IS
O+SIN-1 groups. Myocardial O-2 consumption (ml O-2/min/100 g) was increased
by ISO in CON (10.3 +/- 1.0 to 13.6 +/- 2.0 EPI; 10.9 +/- 1.0 17.1 +/- 1.7
ENDO) and HYP (8.2 +/- 1.4 to 12.3 +/- 2.2 EPI; 6.6 +/- 1.4 to 14.8 +/- 1.
8 ENDO). Oxygen consumption was unaffected by SIN-I in CON and HYP animals.
ISO+SIN-1 caused attenuated ISO-induced increases in O-2 consumption in CO
N in EPI and ENDO, and in EPI in HYP. Cyclic GMP (pmol/g) was unchanged by
ISO in CON and HYP, and increased by SIN-1 in CON (8.1 +/- 1.3 to 19.2 +/-
2.3 EPI) and HYP (9.1 +/- 1.5 to 12.8 +/- 2.0 EPI). Cyclic GMP remained ele
vated with ISO+SIN-1 in both groups. Cyclic AMP (pmol/g) was increased sign
ificantly by ISO in CON (496 +/- 43 to 725 +/- 106 EPI; 534 +/- 44 to 756 /- 148 ENDO) and insignificantly in HYP (435 +/- 50 to 566 +/- 35 EPI; 497
+/- 51 to 583 +/- 47 ENDO). Cyclic AMP levels were unaffected by SIN-1 in e
ither group. Isoproterenol induced increases in cyclic AMP were blunted by
ISO+SIN-1 in CON (496 +/- 43 to 537 +/- 59 EPI) and not affected in HYP. Th
e current study demonstrated attenuation of cyclic AMP mediated increased i
notropy and O-2 consumption by increasing cyclic GMP, which appeared, in pa
rt, related to cyclic GMP-induced reduction in cyclic AMP. This effect of c
yclic GMP on cyclic AMP was not observed in myocardial hypertrophy.