Reduced myocardial cyclic GMP increases myocardial O2 consumption in control but not renal hypertension-induced cardiac hypertrophy.
OBJECTIVE
We tested the hypothesis that a reduction in myocardial cyclic GMP would increase myocardial O2 consumption and that renal hypertension (One Kidney-One Clip, 1K1C)-induced cardiac hypertrophy would change this relationship.


METHODS
Either vehicle or LY83583 (10(-3) M, a guanylate cyclase inhibitor) was topically applied to the left ventricular surface of control of 1K1C anesthetized open-chest New Zealand white rabbits (N = 38). Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to determine subepicardial (EPI) and subendocardial (ENDO) O2 consumption and myocardial cyclic GMP was determined by radioimmunoassay.


RESULTS
The heart weight/body weight ratio was greater in the 1K1C rabbits (3.16 +/- 0.20) than controls (2.58 +/- 0.08 g/kg). Systolic blood pressure was higher in 1K1C rabbits (116 +/- 8 mm Hg) than controls (80 +/- 6), but topical LY83583 had no significant hemodynamic effects. LY83583 significantly and similarly decreased EPI cyclic GMP in both control (7.9 +/- 1.2 to 6.0 +/- 1.0 pmol/g) and 1K1C (7.7 +/- 1.2 to 5.3 +/- 0.9) hearts and control ENDO (8.7 +/- 1.7 to 7.2 +/- 1.2) but not 1K1C ENDO (6.7 +/- 0.5 to 5.7 +/- 1.1). Myocardial O2 consumption was significantly increased in control with LY83583 (EPI 6.6 +/- 1.1 to 15.6 +/- 1.4 and ENDO 7.2 +/- 0.9 to 14.2 +/- 0.7 ml O2/min/100 g), but not in 1K1C hearts (EPI 12.1 +/- 1.0 to 12.9 +/- 1.2 or ENDO 11.4 +/- 0.7 to 12.9 +/- 0.9).


CONCLUSIONS
Thus myocardial O2 consumption was only increased by LY83583 in control hearts, but LY83583 decreased cyclic GMP similarly in both the control and 1K1C EPI. This indicated, at least in the EPI, a dissociation of the inverse relationship between the myocardial level of cyclic GMP and O2 consumption in the 1K1C rabbit heart.
Sadoff
J D
JD
Department of Physiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA.
Scholz
P M
PM
Tse
J
J
Weiss
H R
HR
D000634:Aminoquinolines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism*; D003326:Coronary Circulation / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006977:Hypertension, Renal / Q000150:complications* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010496:Pericardium / Q000378:metabolism; D011817:Rabbits
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; C041715:6-anilino-5,8-quinolinedione; D006162:Guanylate Cyclase; D006152:Cyclic GMP