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Am J Physiol Regul Integr Comp Physiol 286: R678-R685, 2004; doi:10.1152/ajpregu.00419.2003
0363-6119/04 $5.00
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LOCAL CONTROL OF CIRCULATION

Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout

Ryan A. Dombkowski,1,2 Michael J. Russell,1,2 and Kenneth R. Olson1,2

1Department of Biological Sciences and 2South Bend Center for Medical Education, Indiana University School of Medicine, University of Notre Dame, Notre Dame, Indiana 46556

Submitted 25 July 2003 ; accepted in final form 15 December 2003

Hydrogen sulfide (H2S) is an endogenous vasodilator in mammals, but its presence and function in other vertebrates is unknown. We generated H2S from NaHS and examined the effects on isolated efferent branchial arteries from steelhead (stEBA) or rainbow (rtEBA) trout. H2S concentration was measured colorimetrically (CM) and with ion-selective electrodes (ISE) in rainbow trout plasma. NaHS produced a triphasic response consisting of a relaxation (phase 1), constriction (phase 2), and relaxation (phase 3) in both unstimulated vessels and in stEBA precontracted with carbachol (Carb). Phase 1 and phase 3 in stEBA were decreased and phase 2 increased in unstimulated vessels by K+ATP channel inhibition (glibenclamide), or a cocktail of inhibitors of cyclooxygenase, lipoxygenase, and cytochrome P-450 (indomethacin, esculetin, and clotrimazole). Inhibition of soluble guanylate cyclase with ODQ or NS-2028 inhibited phase 3 in stEBA, although NaHS decreased cGMP production by rtEBA. stEBA phase 2 contractions were partially inhibited by the myosin light chain kinase inhibitor, ML-9, but unaffected by L-type calcium channel inhibition (methoxyverapamil), whereas contraction in rtEBA was partially inhibited by nifedipine or removal of extracellular calcium. Phase 3 relaxations were more pronounced in stEBA precontracted with Carb and norepinephrine (NE) than those contracted by KCl or K2SO4. stEBA phase 2 and phase 3 responses were dose dependent (EC50 = 1.1 ± 1.2 x 10-3 M and 6.7 ± 0.9 x 10-5 M, respectively; n = 7). NaHS was also vasoactive in steelhead bulbus arteriosus, celiacomesenteric arteries, and anterior cardinal veins. Rainbow trout plasma sulfide concentration was 4.0 ± 0.3 x 10-5 M, n = 4 (CM) and 3.8 ± 0.4 x 10-5 M, n = 9 (ISE); similar to phase 3 EC50. Because NaHS has substantial vasoactive effects at physiological plasma concentrations, we propose that its soluble derivative, H2S, is a tonically active endogenous vasoregulator in trout.

fish; cardiovascular; guanosine 3',5'-cyclic monophosphate; vasodilator; vasoconstrictor



Address for reprint requests and other correspondence: K. R. Olson, South Bend Center for Medical Education, B-19 Haggar Hall, Univ. of Notre Dame, Notre Dame, IN 46556 (E-mail: kolson{at}nd.edu).




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