Objective: To determine whether chronic renal failure (CRF) reduces nitrergic relaxant responses in a rabbit model.
Materials and methods: Ten rabbits underwent surgery to induce uraemia (CRF rabbits) and a further 10 a sham operation (controls). Corpus cavernosal tissue was prepared and used in organ-chamber experiments, with relaxation assessed against a background of pre-contraction with phenylephrine. At the plateau of contraction, relaxation responses to cumulative concentrations of carbachol or sodium nitroprusside (SNP), to test endothelium-dependent and -independent relaxations, respectively, were assessed. Before electrical-field stimulation (EFS), the tissue was treated with an adrenergic nerve blocker and a muscarinic receptor blocker to eliminate the adrenergic and cholinergic components, and to determine the relaxation responses to the stimulation of nonadrenergic, noncholinergic (NANC) nerves. The relaxation responses in corporal strips obtained from CRF rabbits were compared with those from controls.
Results: When tissues were contracted with KCl, tensions were similar in all groups. The impairment in concentration-dependent relaxation with carbachol was significant in CRF rabbits, but SNP- and papaverine-induced concentration-dependent relaxation responses were no different among the groups. EFS-induced frequency-dependent relaxations were significantly lower in CRF rabbits than in controls.
Conclusion: CRF inhibits the NANC-mediated relaxation of rabbit corpus cavernosum smooth muscle. Changes in NANC-mediated and carbachol-induced (endothelium-dependent) relaxation of corporal smooth muscle in the rabbit are probably caused by uraemia and subsequently, hyperthyroidism, hyperparathyroidism or low testosterone levels in CRF. These results also suggest that if vasoactive agents are to be used for treating erectile dysfunction in uraemic patients, direct-acting vasodilators and phosphodiesterase inhibitors will be useful.