Effects of Some Calcium Channel Blockers on Isolated Human Penile Erectile Tissues

Abstract

The effects of the calcium channel blockers (CCBs) verapamil, nifedipine and diltiazem on contractile activation of isolated human penile erectile tissues were investigated. Specimens of the corpus spongiosum (CS) and corpora cavernosa (CC) were obtained from men with a history of normal penile erection undergoing cystourethrectomy because of bladder malignancy. Preparations were mounted in organ baths and isometric tension was recorded. Deprivation of extracellular calcium abolished electrically induced contractions in both CS and CC preparations within 15 min.; norepinephrine (NE)-induced contractions were reduced by 90% (CS) and 83% (CC) after 30 min. All the CCBs reduced electrically induced contractions concentration-dependently, nifedipine being the most potent agent. Contractions induced by exogenous NE were depressed by about 50%, whereas high K+ (124 mM) induced responses were abolished. It is concluded that contraction in penile erectile tissues is mediated mainly by neuronally released NE stimulating postjunctional alpha-adrenoceptors. The contraction is highly dependent on extracellular calcium and can partly be inhibited by CCBs. It cannot be excluded that some CCBs injected intracavernosally may be useful for diagnosis and even treatment of erectile dysfunction. However, calcium channel blockade may not be as effective as a therapeutic principle as blockade of alpha-adrenoceptors.

The promise of inhibition of smooth muscle tone as a treatment for erectile dysfunction: where are we now?

“…[144][145][146] However, a recent double-blind, randomized study, involving 1549 patients, failed to reveal any significant effect of an Ang-II receptor blockers or an ACE inhibitor on ED. 148,149 CSM contracted by a-adrenergic agonists in vitro. However, ICI of CCBs in dogs was less effective and had more side effects compared to papaverine.…”

“…153,154 Although the side effect of ICI of CCBs was comparable to other agents, CCBs may not be as effective as blockade of a-adrenoceptors. 148,153,154 Blockage of Ca 2 þ -sensitizing pathway (mainly RhoA/ROCK). Ten years ago, the inhibition of ROCK by ICI of Y-27632 was found to induce an erectile response in rats.…”

A survey of commonalities relevant to function and dysfunction in pelvic and sexual organs

“…13,14 Spontaneous contractions (Figure 2a) have been recorded from corpus cavernosum smooth muscle (CCSM) and corpus spongiosum smooth muscle from various mammals, including man. [14][15][16] The mechanisms underlying these contractions are spontaneous action potentials and associated transient increases in [Ca 2 þ ] i (Figures 2b and c) The contractions depend on extracellular Ca 2 þ , and are blocked by L-type Ca 2 þ channel blockers, and by drugs, which hyperpolarize the cells, demonstrating the important role of L-type Ca 2 þ channels in the generation of spontaneous activity.…”

Abanoquil, a new alpha-1 adrenoceptor antagonist. In vitro and in vivo effect on erectile tissue

“…5,6 In the ongoing search for agents that have the capacity of relaxing cc smooth muscle cells and thereby have a possible role in the pharmacological treatment of erectile dysfunction, multiple, in vivo and in vitro studies on cc smooth muscle have been carried out. These studies have demonstrated relaxatory response of cc smooth muscle to naturally occuring compounds such as prostaglandin, 7 vasoactive intestinal polypeptide 8 and pharmacological agents such as papaverine, 9 phosphodiesterase inhibitors, 10 calcium channel blocking compounds, 11 potassium channel openers 12,13 and alpha adrenoceptor blocking agents. 14,15 Abanoquil, UK-52,046 (4-amino-6,7-dimethoxy-2(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinol-2-yl) quinoline methanesulphonate) ( Figure 1) is a novel alpha adrenoceptor antagonist with a high selectivity to the alpha-1 subtype.…”