Xq. Guo et al., ACTION OF ACETYLCHOLINE ON REGIONAL MYOCARDIAL WORK AND METABOLISM IN-VIVO - ASSOCIATION WITH CYCLIC-GMP, Canadian journal of physiology and pharmacology, 74(1), 1996, pp. 73-79
This study was designed to test the hypothesis that in the in vivo dog
heart, increases in cyclic (c) GMP and also decreases in cAMP induced
by intracoronary administration of acetylcholine are associated with
depressed myocardial function. In 10 open-chest anesthetized dogs, 0.5
mu g . kg(-1). min(-1) of acetylcholine was infused into the left ant
erior descending coronary artery. The intracoronary infusion of acetyl
choline was continued simultaneously with 0.1 mu g . kg(-1). min(-1) o
f isoproterenol. Regional segment work was calculated as the integrate
d product of force (auxotonic force transducer) and segment shortening
(sonomicrometry). Regional myocardial O-2 consumption was calculated
from blood flow measurements and regional O-2 saturations. Competitive
radioligand binding assays were used to determine the intracellular l
evel of cAMP and cGMP in the myocardium. Local intracoronary infusion
of acetylcholine significantly reduced regional segment work (from 36.
7 +/- 6.5 to 19.1 +/- 3.7 x 10(-3) J/min) and O-2 consumption (from 6.
4 +/- 0.8 to 3.8 +/- 0.7 mt O-2 . min(-1). 100 g(-1)). This was relate
d to a decrease in cAMP levels (from 364 +/- 25 to 262 +/- 17 pmol/100
g) and an increase in cGMP levels (from 1.34 +/- 0.06 to 1.78 +/- 0.1
5 pmol/100 g). When isoproterenol (0.1 mu g . kg(-1). min(-1)) was add
ed to the acetylcholine infusion line, cAMP levels tripled to 769 +/-
84 pmol/100 g, while O-2 consumption rose to 6.6 +/- 1.4 mt O-2 . min(
-1). 100 g(-1). However, regional work was only partially restored (25
.7 +/- 4.8 x 10(-3) J/min). Thus, both cAMP decrements and cGMP elevat
ion occurred together with the negative inotropic effect of acetylchol
ine, and increased cAMP alone (produced by isoproterenol) did not full
y overcome the acetylcholine effect. This was associated with elevated
intracellular levels of cGMP.