Aim: 

Erectile dysfunction is highly prevalent in men with type 2 diabetes. An increased production of cyclooxygenase 2 (COX-2)-derived contractile prostanoids seems to underlie the abnormal vascular reactivity observed in type 2 diabetes. The aim of the current study was to investigate the vasoactive actions of arachidonic acid (AA) in penile arteries of prediabetic obese Zucker OZR) compared to lean Zucker rats (LZR).

Methods: 

Penile arteries from OZR and LZR were mounted in microvascular myographs. Specific inhibitors of COX-1 (SC-560) and COX-2 (NS-398) were evaluated on the responses to arachidonic acid (AA), acetylcholine (ACh) and noradrenaline (NA).

Results: 

AA elicited relaxations which were impaired in OZR compared with LZR. Inhibition of COX-1 blocked AA relaxant effect at low doses in LZR, but augmented the relaxations at high doses in both LZR and OZR. Selective blockade of COX-2 also inhibited AA relaxant effect at low doses in LZR, but markedly increased relaxations to AA in OZR. SC-560 inhibited relaxations to ACh in penile arteries from LZR but not from OZR, but NS-398 did not affect the relaxatios to ACh in either LZR or OZR. Contractile responses elicited by NA were unaltered by treatment with the COX-1 inhibitor from either LZR or OZR, but they were significantly enhanced by the COX-2 inhibitor in LZR. Immunohistochemical staining showed that COX-1 was localized in the endothelial layer and Western blot analysis revealed a slightly higher expression of COX-2 protein in OZR compared with LZR.

Conclusion: 

Both COX-1 and COX-2 play a role in the physiological regulation of penile arteries through the balanced production of constrictor and dilator prostanoids. There is a production of vasodilator prostanoids through both COX-1 and COX-2 in LZR which is lost in OZR. An enhanced COX-2-dependent production of vasoconstrictor prostaglandins occurs in OZR. Supported by grant SAF2006-09191