Contraction coupled endothelial nitric oxide release: a new paradigm for local vascular control?

Nitric oxide (NO), a potent vasodilator, is presumed to be constitutively released in most mammalian blood vessels. In isolated rat thoracic aorta, however, hemoglobin (Hb), a nitric oxide scavenger, elicited contraction only when the vessels were precontracted with an alpha adrenergic agonist. Does vascular contraction induce endothelial NO release?

Thoracic aortic rings from male Sprague-Dawley rats were prepared with or without the endothelium. Vessel rings were contracted with several distinct types of contractile agonists and NO release was probed using a Hb contraction assay in the presence and absence of nitro-l-arginine methyl ester (NAME), a NO synthase inhibitor.

In vessel rings precontracted with norepinephrine, potassium chloride, arginine vasopressin, prostaglandin F(2alpha), or serotonin, Hb elicited significant additional contractions. In contrast, Hb failed to elicit significant contractions in vessel rings without the functional endothelium or vessels pretreated with NAME. The Hb mediated additional contraction was not inhibited by calmidazolium, a calmodulin antagonist, and protein kinase inhibitors staurosporine and 2,5-dihydromethylcinnamate. Intercellular gap junction inhibitor 2,3-butanedione monoxime at a low dose (<2 mM) significantly attenuated the NE/Hb mediated contractions but at a high dose (>15 mM) completely prevented both contractions. The contraction coupled NO release may be mediated through a mechanism distinct from the Ca(2+)-calmodulin-dependent endothelial NOS pathway.

In the isolated rat thoracic aorta, endothelial NO release may be coupled to contractile stimulus. This vascular property appears to render a unique local control mechanism independent of baroreflex and other central mechanisms.