Guanylyl cyclase mediates ANP-induced vasoconstriction of murine splenic vessels.
We have previously shown that ANP causes differential constriction of the splenic vasculature of the rat (veins greater than arteries), which may be inhibited by blocking the production of cGMP with A7195. In this paper, we report experiments done on vessels derived from guanylyl cyclase (GC)-A knockout mice. Small splenic arteries ( approximately 150-microm diameter) and veins ( approximately 250-microm diameter) were dissected from male GC-A-deficient 129sv mice or age-matched wild-type controls and mounted in a wire myograph. In the wild-type mice, ANP exhibited higher potency in the veins than in the arteries (EC(50) values wild-type mice: artery, 8 +/- 3 x 10(-9) M, n = 5 vs. vein, 6 +/- 4 x 10(-10) M, n = 5; P < 0.05). The concentration-response curve for ANP-induced vasoconstriction was also shifted leftward in denuded compared with intact arteries (EC(50) values: denuded artery: 5 +/- 3 x 10(-10) M, n = 5 vs. intact artery, 8 +/- 3 x 10(-9) M, n = 5; P < 0.05), i.e., the denuded vessels were more reactive. By contrast, ANP caused no significant change in tension from baseline in intact splenic arteries, intact splenic veins, or denuded splenic arteries derived from the GC-A-deficient mice, although these vessels did show normal concentration-dependent increases in tension to phenylephrine. We conclude that ANP causes vasoconstriction in the splenic vasculature by an endothelium-independent mechanism, mediated via guanylyl cyclase.
Andrew
Peter S
PS
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Kaufman
Susan
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010656:Phenylephrine / Q000494:pharmacology; D013154:Spleen / Q000098:blood supply*; D013157:Splenic Artery / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D013162:Splenic Vein / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase