Comparative studies on intracellular calcium and NADH Fluorescence of the rabbit corpus cavernosum

Erectile function (erection and detumescence) involves the complex interaction of direct neuronal stimulation of corporal smooth muscle, neurohumoral release of specific endothelial contractile and relaxant factors, and secondary modulation by a variety of putative neuropeptides and vasoactive modulators. Using surface spectrofluorometry, we have correlated spontaneous contractile activity and the contractile response to field and pharmacological agents with intracellular calcium and NADH metabolism. The results demonstrate that the corpus cavernosal tissue has very unusual properties. Spontaneous contractile activity is correlated with a phasic increase in intracellular calcium. However, spontaneous contractile activity is most often correlated with a bi-phasic effect on the ratio of NADH/NAD. At the start of the spontaneous contraction, there is a sharp phasic increase in NADH/NAD; peak contractile force occurs simultaneous with a phasic decrease in this ratio showing that at peak force generation, there is a decrease in the level of intracellular energy. Phenylephrine stimulation results in an increase in intracellular calcium in proportion to the increase in tension; however, phenylephrine stimulation at low concentrations results in a net increase in the NADH/NAD ratio whereas high concentrations of phenylephrine result in a net decrease in the NADH/NAD ratio. In general, field stimulation results in a decrease in tension at low frequencies, a biphasic response at midfrequencies, and a contraction at high frequencies. These contractile responses are directly directly related to alterations in the intracellular concentration of calcium. That is, a decrease in tension is preceded by a decrease in intracellular calcium while an increase in tension is preceded by an increase in intracellular free calcium. Field stimulation results in a rapid and phasic alteration in the NADH/NAD ratio; however, the NADH/NAD response can be either an increase, decrease, or biphasic response. There does not appear to be a consistent relationship between the contractile/relaxant response to field stimulation and altered NADH/NAD ratio. Finally, ATP, bethanechol, and nitroprusside induce a decrease in the basal tension of the corpus cavernosal strips which corresponds with a decrease in the NADH/NAD ratio. However, whereas nitroprusside relaxation is correlated with a decreased intracellular calcium level, both ATP and bethanechol stimulate an increase in intracellular free calcium. These studies indicate that the response of the corpus cavernosal tissue to both field stimulation and pharmacological agents is complex and may involve both direct and indirect actions of a variety of cellular mediators on the corporal smooth muscle.