CHARACTERIZATION OF CALCIUM-CHANNEL BLOCKER INDUCED SMOOTH-MUSCLE RELAXATION USING A MODEL OF ISOLATED CORPUS CAVERNOSUM

Several classes of smooth muscle relaxing agents have proven effective in relaxing cavernosal smooth muscle and useful in the pharmacotherap y of erectile dysfunction. The purpose of this investigation was to de termine whether the calcium channel blockers (CCB) relax cavernosal sm ooth muscle. Thirty-two rabbit cavernosal strips were contracted by el ectrical field stimulation, and contraction inhibition was tested in r esponse 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 elect rically induced contractions (p <0.0001 when CCB was compared with con trol; p <0.05 when V or D was compared with I, Nc or Nf). Sixteen cave rnosal strips were precontracted with 10(-5) M. norepinephrine. Relaxa tion in response to cumulative doses of each CCB was determined. Verap amil 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 w hen V, I, Nc, or Nf was compared with control). Sixteen cavernosal str ips were incubated in solutions of 10(-5) and 10(-4) M. of each CCB fo llowed by cumulative addition of norepinephrine (concentration range 1 0(-8) to 10(-4) M.). Preincubation with CCB did not affect the concent ration of norepinephrine at which 50% of maximal cavernosal contractil e response occurred (ED50). Maximum active tension of norepinephrine i nduced contractions was moderately decreased after CCB preincubation w ith 10(-4) M. of each dihydropyridine. It is concluded that the calciu m 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.