Novel role of AQP-1 in NO-dependent vasorelaxation.
Nitric oxide (NO) produced by endothelial cells diffuses to vascular smooth muscle cells to cause dilatation of the renal vasculature and other vessels. Although it is generally assumed that NO moves from cell to cell by free diffusion, we recently showed that aquaporin-1 (AQP-1) transports NO across cell membranes. AQP-1 is expressed in endothelial and vascular smooth muscle cells. We hypothesized that diffusion of NO into vascular smooth muscle cells and out of endothelial cells is facilitated by AQP-1, and transport of NO by AQP-1 is involved in endothelium-dependent relaxation. In intact aortic rings from AQP-1 -/- mice, vasorelaxation induced by acetylcholine (which increases endogenous NO) was reduced (P < 0.0001 vs. control). No differences were found in the relaxation caused by intracellular delivery of NO or intracellular cGMP between strains. In endothelium-denuded aortic rings from AQP-1 -/- mice, the vasorelaxant capability of NO released in the extracellular space was reduced (P < 0.0001 vs. control). Influx of NO (5 microM) into vascular smooth muscle cells was 0.17 +/- 0.02 f.u./s for control and 0.07 +/- 0.01 f.u./s for AQP-1 -/- mice, 62% lower (P < 0.002). NO released by endothelial cells in response to 1 microM acetylcholine was 96.2 +/- 17.7 pmol NO/mg for control and 41.9 +/- 13.4 pmol NO/mg for AQP-1 -/- mice, 56% reduction (P < 0.04). NOS3 expression was 1.33 +/- 0.29 O.D. units for control and 3.84 +/- 0.76 O.D. units for AQP-1 -/- mice, 188% increase (P < 0.01). We conclude that 1) AQP-1 facilitates NO influx into vascular smooth muscle cells, 2) AQP-1 facilitates NO diffusion out of endothelial cells, and 3) transport of NO by AQP-1 is required for full expression of endothelium-dependent relaxation.
Herrera
Marcela
M
Henry Ford Hospital, Division of Hypertension and Vascular Research, Wayne State University, Detroit, Michigan 48202, USA. mherrer1@hfhs.org
Garvin
Jeffrey L
JL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051398:Aquaporin 1 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D004058:Diffusion; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D051398:Aquaporin 1; D009569:Nitric Oxide; D000109:Acetylcholine