Several classes of smooth muscle relaxing agents have proven effective in relaxing cavernosal smooth muscle and useful in the
pharmacotherapy of
erectile dysfunction. The purpose of this investigation was to determine whether the
calcium channel blockers (CCB) relax cavernosal smooth muscle. Thirty-two rabbit cavernosal strips were contracted by electrical field stimulation, and contraction inhibition was tested in response to cumulative doses (10(-8) M. to 10(-4) M.) of
verapamil (V),
diltiazem (D),
isradipine (I),
nicardipine (Nc) and
nifedipine (Nf). All of the
calcium channel blockers were effective at inhibiting electrically induced contractions (p < 0.0001 when CCB was compared with control; p < 0.05 when V or D was compared with I, Nc or Nf). Sixteen cavernosal strips were precontracted with 10(-5) M.
norepinephrine. Relaxation in response to cumulative doses of each CCB was determined.
Verapamil and the
dihydropyridines (
isradipine,
nicardipine and
nifedipine), but not
diltiazem, were effective at relaxing
norepinephrine induced contractions
at 10(-5) and 10(-4) M. with
verapamil most effective
at 10(-4) M. concentration (p < 0.0001 by ANOVA at both concentrations when V, I, Nc, or Nf was compared with control). Sixteen cavernosal strips were incubated in solutions of 10(-5) and 10(-4) M. of each CCB followed by cumulative addition of
norepinephrine (concentration range 10(-8) to 10(-4) M.). Preincubation with CCB did not affect the concentration of
norepinephrine at which 50% of maximal cavernosal contractile response occurred (ED50). Maximum active tension of
norepinephrine induced contractions was moderately decreased after CCB preincubation with 10(-4) M. of each
dihydropyridine. It is concluded that the
calcium channel blockers are effective in relaxing cavernosal smooth muscle and therefore possess potential as intracavernous pharmacotherapeutic agents for the treatment of
erectile dysfunction.
Verapamil appears to be the best candidate for further testing and clinical trial.