Experimental diabetes mellitus inhibits prostacyclin synthesis by the rat penis: pathological implications

Abstract

Summary. In view of the marked increase in blood flow into the penis during erection and the association of diabetes mellitus with impotence, we used the diabetic rat model to investigate the possibility that: (a) the penis may produce prostacydin; and (b) prostacyclin secretion may be decreased in diabetes. Rats given a high dose of streptozotocin (120 mg/kg body weight) developed acute ketotic diabetes and were killed after 48 h. Animals given a low dose of streptozotocin (65 rag/ kg body weight) developed non-ketonuric diabetes and were killed after 7 or 62 days. Aortic rings and penile tissue discs were incubated in buffer, which was assayed for 6-oxo-prostaglandin Fla, the stable and spontaneous breakdown product of prostacyclin. Penile tissue from control, ketotic and non-ketonuric (7 days) animals released similar quantities of prostacyclin, whereas that from long-term non-ketonuric animals (62 days) produced significantly less prostacyclin. Production of this prostanoid by the aortic rings paralleled these changes. We conclude that: (a) penile tissue releases prostacyclin in quantities comparable to those of the aorta; (b) long-term diabetes leads to diminished prostacyclin release by penile and aortic tissue: the former may contribute to the pathogenesis of diabetic impotence; and (c) since short-term ketotic diabetes does not inhibit aortic or penile prostacyclin release, duration of diabetes rather than its severity is responsible for diminished prostacyclin release.

Reactive oxygen species and erectile dysfunction: possible role of NADPH oxidase

“…185,186 It was demonstrated some time ago that the formation of PGI 2 in cavernosal tissue is reduced in conditions that predispose to ED. [187][188][189][190][191] The administration of PGI 2 analogues, such as iloprost, have long been known to elicit vasculoprotective effects. 192 The administration of the PGI 2 analogue, beraprost, prevented the development of severe neuropathy in diabetic rats.…”

Noncholinergic Penile Erection in Mice Lacking the Gene for Endothelial Nitric Oxide Synthase

“…Organ bath experimentation involving the application of various putative eNOS agonists to isolated erectile tissue provides a basic strategy to investigate this issue, although the approach has generally relied on mechanical removal of endothelium and then inference as to how the tissue relaxation effects are altered in its absence. Problems inherent in this approach are the inconsistency of endothelium removal and, more importantly, the inability to discern whether the altered physiology is due to eNOS absence or absence of other possibly active vasodilators such as prostacyclin (Jeremy et al, 1985) released from the endothelium. The application of NOS inhibitors to assess eNOS biology is also deemed problematic because of nonselective inhibitory effects on other NOS isoforms such as nNOS.…”

Autoradiographic Localization of Nitric Oxide Synthase Binding Sites in Normal and Diabetic Rat Corpus Cavernosum

“…This finding should be considered in the light of pre vious studies which suggested that a relatively short peri od of diabetes causes alterations in the physiological mechanisms that modulate corpus cavemosal smooth muscle relaxation [3][4][5], an essential step for penile erec tion.…”

“…We also identified changes brought about by the onset of diabetes mellitus (DM), a common cause of erec tile dysfunction in both the rat model [5] and man [1], bitone (Sagatal; May and Baker, Dagenham, UK). Their penile tis sues were excised and stored immediately at -70° C in airtight cryotubes.…”

“…Animal models have the advantage of standardized diet, disease duration, medication, as well as tissue availability. The rat penis has also been shown to be a good model of human function [4,5].…”