Hydrolysis of cyclic guanosine monophosphate and cyclic adenosine monophosphate by the penis and aorta of the diabetic rat.

Abstract

To investigate the hydrolysis of adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) by specific phosphodies-terases (PDEs) in the penis and aorta of diabetic rats. Non-ketonuric diabetes mellitus was induced in 10 Sprague-Dawley rats with streptozotocin. After 2 months, the rats were killed and their penises and aortae excised. The tissues were incubated with [3H]-cAMP and [3H]-cGMP and the degree of hydrolysis was assessed by separating [3H]-cAMP and [3H]-cGMP from [3H]-AMP and [3H]-GMP, respectively, in the incubation supernatants using thin layer chromatography (polyethyleneimine cellulose developed in 50 mmol/L KCl). The hydrolysis of cAMP and cGMP was significantly reduced in penile and aortic tissue from diabetic rats compared to that of seven age-matched controls. Such a reduction of PDE activity would result in increased intracellular cyclic nucleotide levels (and thus corporeal smooth muscle relaxation and erection). Consequently, the altered activity of PDE enzyme systems is not related aetiologically to the pathogenesis of diabetic erectile dysfunction. Furthermore, these data consolidate the concept that enhanced cyclic nucleotide synthesis and decreased degradation constitute an adaptive response to counteract the deleterious effects of diabetes mellitus on erectogenic mechanisms. The pathophysiology and therapeutic implications of these findings warrant further investigation.