Ja. Hypolite et al., CORRELATION OF CONTRACTILE FUNCTION OF THE RABBIT CORPUS CAVERNOSUM WITH NADH FLUORESCENCE, Pharmacology, 46(6), 1993, pp. 353-361
The NADH/NAD ratio is a measure of potential metabolic energy in smoot
h muscle tissue. Previous studies on bladder smooth muscle demonstrate
d that during active contraction when energy utilization is high, NADH
is rapidly oxidized to NAD resulting in a decrease in the ratio of NA
DH/NAD. Intracellular systems utilizing ATP as an energy source are ch
aracterized by changes in the NADH/NAD ratio. This ratio can be monito
red simultaneously with changes in smooth muscle tissue tone using an
optical fiber probe which continually monitors NADH fluorescence and c
ontractile activity of the same smooth muscle preparation. The present
study correlates alterations in the ratio of NADH/NAD with both spont
aneous and induced contractions and relaxations in the rabbit corpora
cavernosa. The results show a high degree of correlation between a dec
rease in spontaneous fluorescence (decrease in the NADH/NAD ratio) and
spontaneous contraction. An increase in tension was followed in time
by a decrease in the NADH/NAD ratio. This was consistent for all strip
s showing significant spontaneous activity. ATP caused a rapid decreas
e in tension which was correlated with a decrease in fluorescence. The
relative decrease in NADH fluorescence was proportional to the relati
ve decrease in tension. Under basal conditions (0.8 g passive tension)
ATP and nitroprusside stimulated a marked reduction in tension, but o
nly ATP stimulated a substantial decrease in NADH fluorescence. Bethan
echol and isoproterenol relaxed the corporal tissue to a relatively sm
all degree which correlated with relatively small decreases in fluores
cence. Methoxamine stimulated a substantial contraction of corporal sm
ooth muscle which correlated with a rapid and significant decrease in
NADH fluorescence. Following precontraction by methoxamine, ATP stimul
ated a marked decrease in both tension and fluorescence. Nitroprusside
and bethanechol similarly stimulated marked decreases in tension with
only minor changes in NADH fluorescence. Isoproterenol induced a mino
r decrease in tension with no significant change in NADH fluorescence
from that of the basal response. The dissociation of the endothelium f
rom the corporal tissue inhibited the response to bethanechol by 90% f
or both fluorescence and tension while the response to ATP was virtual
ly unaffected. In summary, the data indicate a strong correlation betw
een stimulation of contraction by methoxamine and a decrease in the NA
DH/NAD ratio; and strong relaxation of corporal smooth muscle by ATP a
nd a decrease in the NADH/NAD ratio. Since these drugs have opposite e
ffects on tension, this result may indicate that both contraction- and
ATP- induced relaxation in the rabbit corpus cavernosa are active pro
cesses and depend on the rapid utilization of cellular metabolic energ
y. It appears that corporal relaxation mediated by nitroprusside is hi
ghly efficient, utilizing significantly less intracellular energy and
producing maximal relaxations.