The effect of intracoronary nitroprusside on cyclic GMP and regional mechanics is altered in a canine model of left ventricular hypertrophy.
Nitroprusside can produce negative inotropy by activating cGMP. We hypothesized that in left ventricular hypertrophy produced by aortic valve plication (LVH), control of myocardial work and metabolism by cGMP production would be altered in response to nitroprusside. In anesthetized open chest preparations using 9 LVH and 12 control dogs, nitroprusside (4 micrograms/kg/min) was infused into the left anterior descending coronary artery. The circumflex (CFX) region served as an internal control. Segment force (miniature gauge) and length (sonomicrometer) were measured in both regions. Segment work was calculated as the integrated products of local force and segment shortening. Regional myocardial O2 consumption was calculated from blood flow measurements (radioactive microspheres) and regional O2 saturations (microspectrophotometry). Radioimmunoassay was used to determine regional cGMP levels. In control dogs, nitroprusside significantly reduced force in the treated region (from 10.3 +/- 0.8 to 7.9 +/- 0.9 g) and segment work (from 1889 +/- 296 to 1254 +/- 252 g.mm/min). In the LVH group, regional work, force, and shortening did not change. In the CFX regions of both groups, regional myocardial mechanics, as well as regional myocardial O2 consumption, were not altered during nitroprusside infusion. Cyclic GMP levels were elevated to a much greater extent in the LVH animals (from 3.26 +/- 0.60 to 15.23 +/- 4.65 pmole/g) than in the control animals (from 2.16 +/- 0.60 to 2.89 +/- 0.56 pmole/g). Thus, in contrast to control myocardium, significant increases in cGMP production during nitroprusside infusion failed to produce negative inotropy in LVH. These findings suggest an uncoupling between the second messenger and systems controlling muscle contraction.
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903-0019.
A
A
Roitstein
J
J
Kedem
B
B
Cheinberg
H R
HR
Weiss
J
J
Tse
P M
PM
Scholz
D000818:Animals; D001783:Blood Flow Velocity; D003331:Coronary Vessels / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D006321:Heart / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D009599:Nitroprusside / Q000494:pharmacology*; D010101:Oxygen Consumption; D011863:Radioimmunoassay; D012039:Regional Blood Flow / Q000502:physiology
D009599:Nitroprusside; D006152:Cyclic GMP