Impairment of endothelium- and nerve-mediated relaxation responses in the cavernosal smooth muscle of experimentally diabetic rabbits: role of weight loss and duration of diabetes

Abstract

The effects of short- and long-term experimental diabetes on corporal nerve, endothelium and smooth-muscle responses were investigated, and the reasons for possible alterations in corporal smooth muscle responses such as hyperglycaemia, duration of experimental diabetes and/or altered tissue weight were evaluated. Rabbits were injected with alloxan (125 mg/kg) to induce diabetes. Age-matched non-diabetic and diabetic (3 and 9 weeks) and weight-matched non-diabetic groups (9 weeks) were used as control. In all groups, relaxation (carbachol, electrical field stimulation and sodiumnitroprusside) responses were examined. The relaxation responses were expressed as percentage of the precontraction to phenylephrine and as g response/g tissue weight. The effects of elevated glucose were also examined by incubating cavernosal strips in Krebs-Henseleit solution containing 44.4 mM glucose for 6 h. Cavernosal tissues of non-diabetic and 9-week diabetic rabbits were evaluated histologically. Sodiumnitroprusside (10(-7)-10(-4) M) responses were similar in all groups. Relaxation responses to electrical field stimulation (10 s train; amplitude 50 V; frequency 0.5-32 Hz; width 0.8 ms) were only attenuated in the 9-week diabetic group compared to the non-diabetic group. Carbachol (10(-8)-3 x 10(-5) M) responses were attenuated in both diabetic groups. When the relaxation responses expressed as g response/g tissue weight were evaluated, results were similar compared to those expressed as percentage of phenylephrine (10(-5) M). Neither carbachol nor electrical field stimulation mediated responses were impaired with glucose incubation. No morphological degenerations were observed in the endothelium. Diabetes may interfere with the synthesis and/or release of nitric oxide from both nerves and endothelium in corpus cavernosum, and alterations in endothelium-derived responses occur earlier than neurological disturbances. The sensitivity of cavernosal smooth muscle to nitric oxide did not alter in diabetes. Attenuation of responses was not due to decreased tissue weight caused by diabetes.