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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/H1319    most recent 00039.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bohlen, H. G. Articles by Zawieja, D. PubMed PubMed Citation Articles by Bohlen, H. G. Articles by Zawieja, D.

Phasic contractions of rat mesenteric lymphatics increase basal and phasic nitric oxide generation in vivo

¹Department of Cellular and Integrative Physiology, Indiana University Medical School, Indianapolis, Indiana; and ²Department of Systems Biology and Translational Medicine, Texas A&M Health Science Center College of Medicine, Temple, Texas

Submitted January 12, 2009 ; accepted in final form June 15, 2009

Multiple investigators have shown interdependence of lymphatic contractions on nitric oxide (NO) activity by pharmacological and traumatic suppression of endothelial NO synthase (eNOS). We demonstrated that lymphatic diastolic relaxation is particularly sensitive to NO from the lymphatic endothelium. The predicted mechanism is shear forces produced by the lymph flow during phasic pumping, activating eNOS in the lymphatic endothelium to produce NO. We measured [NO] during phasic contractions using microelectrodes on in situ mesenteric lymphatics in anesthetized rats under basal conditions and with an intravenous saline bolus (0.5 ml/100 g) or infusion (0.5 ml·100 g^–1·h^–1). Under basal conditions, [NO] measured on the tubular portions of the lymphatics was 200–250 nM, slightly higher than in the adjacent adipocyte microvasculature, whereas [NO] measured on the lymphatic bulb surface was 400 nM. Immunohistochemistry of eNOS in isolated lympathics indicated a much greater expression in the lymph valves and surrounding bulb area than in the tubular regions. During phasic lymphatic contractions, the valve and tubular [NO] increased with each contraction, and during intravenous saline infusion, [NO] increased in proportion to the contraction frequency and, presumably, lymph flow. The partial blockade of eNOS over 1 cm length with N-nitro-L-arginine methyl ester lowered the [NO]. These in vivo data document for the first time that both valvular and tubular lymphatic segments increase NO generation during each phasic contraction and that [NO] summated with increased contraction frequency. The combined data predict regional variations in eNOS and [NO] in the tubular and valve areas, plus the summated NO responses dependent on contraction frequency provide for a complex relaxation mechanism involving NO.

lymph flow; frequency contraction