When the penis is in the flaccid state, the corpus cavernosum smooth m
uscle is under adrenergic control in order to maintain the sinusoids i
n a contracted condition (primarily via alpha-adrenergic stimulation),
Penile erection is mediated by relaxation of corporal smooth muscle t
hrough a variety of direct and indirect mechanisms. Pharmacological ag
ents that either inhibit alpha-adrenergic transmission or facilitate c
orporal smooth muscle relaxation will be beneficial for penile erectio
n, Preliminary studies on macrocycle 1, a novel bioactive agent, demon
strated that this compound inhibits receptor-stimulated contraction wi
thout significantly altering field-stimulated contraction. The current
study was designed to determine the physiological effects of macrocyc
le 1 on the response of the rabbit corpus cavernosum to various forms
of stimulation. Sexually mature male New Zealand White rabbits were us
ed in this study, The corpus cavernosum was dissected sharply from the
removed penis and two longitudinal strips were prepared for isometric
tension studies. Each strip was prestimulated with 200 mu mol/l pheny
lephrine to produce a maximal contraction. The influences of macrocycl
e 1 (15.6, 62.5, 250, 1,000 mu mol/l) on both the contractile response
to phenylephrine and the relaxant effects of field stimulation. carba
chol, ATP and nitroprusside were determined, The results demonstrated
that although basal tension was not altered, the contractile response
to phenylephrine was decreased by 5, 18, 47 and 57%, respectively, by
the different concentrations of macrocycle 1. The degree of relaxation
induced by field stimulation of various frequencies was significantly
enhanced by macrocycle 1 in a concentration-dependent manner. Similar
ly, the degrees of relaxation induced by bethanechol, ATP and nitropru
sside were all significantly enhanced in a concentration-dependent man
ner. The conclusion from this study is that macrocycle 1 significantly
inhibits phenylephrine-stimulated contraction and significantly enhan
ces field-stimulated and pharmacologically induced relaxation. Althoug
h the mechanisms of action are not clear, its physiological effects on
the rabbit corpus cavernosum implicate a potential for the treatment
of erectile dysfunction.