Objectives: 

Endothelial dysfunction impairs vascular function in cardiovascular diseases as well as in endocrine-metabolic disorders. The present study was focused to explore the role of NO, cyclooxygenase (COX)-derived products and the potassium channels involved in response to an endothelium-dependent agonist such as acetylcholine (ACh) in a prediabetic model of obese rats.

Materials: 

Seventeen-week-old lean (LZRs) and obese Zucker rats (OZRs) were used for all experiments. Femoral artery was cut into ring segments and they were mounted in a multimyograph for isometric force recording.

Results: 

Relaxations in response to ACh were significantly smaller in femoral arteries from OZRs than the LZRs. The relaxation induced by ACh was strongly inhibited by NO synthase and soluble guanylate cyclase inhibition using L-NOArg and ODQ. The selective COX-1 inhibitor, SC-560, but not the selective COX-2 inhibitor, NS-398, diminished vasodilatations to ACh in arteries from LZRs, but did not affect those observed in OZRs. Tetraethylamonium or 4-amynopyridine, the Ca2+-activated (KCa) or voltage-dependent potassium (Kv) channel blockers, respectively, reduced relaxation in LZRs and OZRs. However, the inhibition induced by KCa and Kv channel blockers was significantly greater in arteries from OZRs. The putative gap junction blocker, carbenoxolone, significantly attenuated ACh-mediated relaxation only in obese rat artery.

Conclusions: 

Disruption of relaxant COX-1-derived prostanoid production may contribute to the endothelial dysfunction observed in femoral arteries from OZRs. However, endothelium-derived hyperpolarization mechanisms operating through opening of potassium channels and gap junctions probably act as a backup pathway to exert a protective vasodilator effect by enhancing relaxation to ACh.

This study has been supported by grant nordm; SAF2009-19448 from the Spanish Ministry of Science and Innovation, Spain.