Flow-evoked vasodilation is blunted in penile arteries from Zucker diabetic fatty rats

Olav Lilleholt Schjørring, Attila Kun, Allan Flyvbjerg, Hans Jørgen Kirkeby, Jørgen Bjerggaard Jensen, Ulf Simonsen

12 Citationer (Scopus)

Abstract

INTRODUCTION: Endothelium-derived relaxing factors such as nitric oxide (NO), prostanoids, and endothelium-derived hyperpolarizing factor (EDHF) are thought to play an important role in vasodilation of penile arteries.

AIM: The present study investigated the mechanisms involved in flow- and acetylcholine-induced vasodilation in penile arteries, and whether acetylcholine- and flow-mediated vasodilation is altered in Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes. Moreover, it was addressed whether enhanced myogenic tone may explain impaired flow-evoked vasodilation in arteries from ZDF rats.

METHODS: Penile dorsal arteries obtained from lean control and ZDF rats were suspended in a pressure myograph, and flow- and acetylcholine-evoked vasodilation was measured as changes in arterial diameter.

MAIN OUTCOME MEASURE: Changes in penile arterial diameter.

RESULTS: Incubation with an inhibitor of NO synthase, asymmetric dimethyl-L-arginine (ADMA), and of cyclooxygenase, indomethacin, reduced acetylcholine but not flow-evoked vasodilation in penile arteries, while both responses were abolished by endothelial cell removal. Iberiotoxin, a blocker of large-conductance calcium-activated K+ (BK(Ca) ) channels, inhibited flow-evoked vasodilation. Flow-evoked vasodilation was reduced in arteries from ZDF rats in the absence, but not in the presence, of indomethacin plus ADMA. Elevation of intraluminal pressure increased myogenic tone, which was reduced in arteries from ZDF rats.

CONCLUSION: The present findings show that flow evokes endothelium-dependent EDHF-type vasodilation involving BK(Ca) channels in penile arteries. Flow-evoked vasodilation is reduced and only of EDHF-type in penile arteries from type 2 diabetic rats suggesting modulation of this pathway may restore endothelial function and preserve erection in diabetes.

OriginalsprogEngelsk
TidsskriftThe journal of sexual medicine
Vol/bind9
Udgave nummer7
Sider (fra-til)1789-800
Antal sider12
ISSN1743-6095
DOI
StatusUdgivet - jul. 2012
Udgivet eksterntJa

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