Altered arachidonic acid metabolism via COX-1 and COX-2 contributes to the endothelial dysfunction of penile arteries from obese Zucker rats.
OBJECTIVE
The aim of the current study was to investigate the role of arachidonic acid (AA) metabolism via cyclooxygenase (COX) in the endothelial dysfunction of penile arteries from pre-diabetic, obese Zucker rats (OZR).


METHODS
Penile arteries from OZR and from lean Zucker rats (LZR) were mounted in microvascular myographs to assess vascular function and COX expression was determined by immunohistochemistry.


RESULTS
Acetylcholine (ACh) and AA elicited relaxations that were impaired in arteries from OZR. Inhibition of both COX-1 and COX-2 reduced the relaxant effects of ACh and AA in LZR but not in OZR. Inhibitors of COX-1 and of the TXA(2)/PGH(2) (TP) receptor enhanced the relaxations induced by AA in both LZR and OZR, whereas COX-2 inhibition enhanced these responses only in OZR. TP receptor blockade did not restore ACh relaxant responses in arteries from OZR. Inhibition of COX-1 increased basal tension in OZR and this contraction was blunted by TP receptor blockade. The vasoconstrictor responses to noradrenaline were augmented by indomethacin and by COX-2 inhibition in LZR but not in OZR. Immunohistochemical staining showed that both COX-1 and COX-2 are expressed in the endothelium of penile arteries from both LZR and OZR.


CONCLUSIONS
Vasoactive prostanoids were formed via constitutively active COX-1 and COX-2 pathways in normal rat penile arteries. Under conditions of insulin resistance, the release and/or effects of vasodilator prostanoids were impaired, contributing to the blunted endothelium-dependent vasodilatation and to the enhanced vasoconstriction.
Sánchez
A
A
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Contreras
C
C
Villalba
N
N
Martínez
P
P
Martínez
A C
AC
Bríones
A
A
Salaíces
M
M
García-Sacristán
A
A
Hernández
M
M
Prieto
D
D
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism / Q000502:physiology* / Q000503:physiopathology*; D051545:Cyclooxygenase 1 / Q000378:metabolism / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism / Q000494:pharmacology; D006940:Hyperemia / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance; D008297:Male; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D010413:Penis / Q000378:metabolism / Q000503:physiopathology; D011236:Prediabetic State / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D016718:Arachidonic Acid; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000109:Acetylcholine; D009638:Norepinephrine