Role of endogenous nitric oxide generation in the regulation of vascular tone and reactivity in small vessels as investigated in transgenic mice using synchrotron radiation microangiography

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a centra l role in regulation of vascular tone and reactivity. The purpose of this s tudy is to clarify the basal tone and microvascular reactivity in eNOS-over expressing transgenic (Tg) mice in vivo with a microangiography system usin g monochromatic synchrotron radiation (SR). The mouse femoral artery was ca nnulated, nonionic contrast media was injected, and microangiography was pe rformed in hindlimbs of mice. Serial images of the small blood vessels (dia meter < 200 mum) were recorded by the SR microangiography system. At basal conditions, the diameter of tibial arteries in eNOS-Tg mice was larger than that of wild-type mice (179 +/- 8 versus 132 +/- 8 pm; P < 0.01). L-NAME t reatment decreased the vessel diameter and canceled the difference in vesse l diameters between two genotypes. Acetylcholine- and sodium nitroprusside- induced relaxations of small vessels were significantly reduced in Tg mice compared with wild-type mice (35.0 +/- 9.4 versus 61.6 +/- 6.7%, 85.0 +/- 1 0.2 versus 97.3 +/- 6.7% of the maximum relaxation, respectively). Our data provide the evidence that overproduced NO from endothelium reduces vascula r tone and plays a pivotal role in regulation of vascular tone in small ves sels. Furthermore, the reduced NO-mediated relaxation in small vessels of e NOS-Tg mice is demonstrated for the first time in vivo. SR microangiography allows us to evaluate the reactivity in small-sized vessels and appears to be a powerful tool for assessing the microvascular circulation in vivo. (C ) 2001 Academic Press.