Enhanced nitric oxide signaling amplifies vasorelaxation of human colon cancer feed arteries.
Inadequate perfusion of solid cancer tissue results in low local nutrient and oxygen levels and accumulation of acidic waste products. Previous investigations have focused primarily on tumor blood vessel architecture, and we lack information concerning functional differences between arteries that deliver blood to solid cancer tissue versus normal tissue. Here, we use isometric myography to study resistance-sized arteries from human primary colon adenocarcinomas and matched normal colon tissue. Vasocontraction of colon cancer feed arteries in response to endothelin-1 and thromboxane stimulation is attenuated compared with normal colon arteries despite similar wall dimensions and comparable contractions to arginine vasopressin and K+-induced depolarization. Acetylcholine-induced vasorelaxation and endothelial NO synthase expression are increased in colon cancer feed arteries compared with normal colon arteries, whereas vasorelaxation to exogenous NO donors is unaffected. In congruence, the differences in vasorelaxant and vasocontractile function between colon cancer feed arteries and normal colon arteries decrease after NO synthase inhibition. Rhythmic oscillations in vascular tone, known as vasomotion, are of lower amplitude but similar frequency in colon cancer feed arteries compared with normal colon arteries. In conclusion, higher NO synthase expression and elevated NO signaling amplify vasorelaxation and attenuate vasocontraction of human colon cancer feed arteries. We propose that enhanced endothelial function augments tumor perfusion and represents a potential therapeutic target. NEW & NOTEWORTHY Local vascular resistance influences tumor perfusion. Arteries supplying human colonic adenocarcinomas show enhanced vasorelaxation and reduced vasocontraction mainly due to elevated nitric oxide-mediated signaling. Rhythmic oscillations in tone, known as vasomotion, are attenuated in colon cancer feed arteries.
['Voss|Ninna C S|NCS|', 'Kold-Petersen|Henrik|H|', 'Boedtkjer|Ebbe|E|0000-0002-5078-9279']
D000109:Acetylcholine D000230:Adenocarcinoma D000328:Adult D000368:Aged D000369:Aged, 80 and over D001158:Arteries D003110:Colonic Neoplasms D019332:Endothelin-1 D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D009389:Neovascularization, Pathologic D009569:Nitric Oxide D052250:Nitric Oxide Synthase Type III D015398:Signal Transduction D013931:Thromboxanes D014662:Vasoconstrictor Agents D014664:Vasodilation D014665:Vasodilator Agents
tumor vasocontraction vasomotion endothelium-dependent vasorelaxation resistance arteries