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concentration range over which isolated intact aorta consume H
2
S without exhibiting
inhibition of either O
2
or H
2
S consumption, aorta segments stimulated with phenyle-
phrine to about 50-75% of maximum vasoconstriction to contract were held in the
respirometer at 40 to 50
M O
2
, above the limiting O
2
concentration (called critical
O
2
), and H
2
S was added to titrate both rates (Kraus
et al.
, preliminary data, not shown).
H
2
S stimulated both O
2
and H
2
S consumption until rates became inhibited at higher
H
2
S levels, as was observed with RASMCs. The H
2
S concentration that stimulated
maximal consumption rates, approximately 20
µ
M, is also the concentration that elicits
maximal vasorelaxation of the precontracted aorta (see Fig. 8.11), demonstrating that
H
2
S-mediated vasorelaxation is not the result of inhibited mitochondrial respiration.
µ
8.6.3 Simultaneous measurement of H
2
S level and vessel tension
Demonstration of the rapid relaxation and contraction response of an intact blood vessel
to simulated changes in vascular H
2
S levels was made possible by placing the PHSS in
the organ bath of a vessel bioassay system (Radnoti, Monrovia, CA). At physiologi-
cal O
2
concentrations, rat aortic vessel tension responded to H
2
S in a concentration-
dependent manner, and the magnitude of these responses was highly O
2
dependent
(Fig. 8.11). Moreover, with the use of chemical inhibitors of specifi c signaling path-
ways in the organ bath, it was also possible to demonstrate that H
2
S-mediated changes
in vascular tone resulted from multiple signaling pathways operating at different rates.
Thus, the ability to follow and dissect the complex vascular effects of H
2
S is only pos-
sible with a real-time PHSS.
40 M O
2
1.2
40
100 nM PE
1
30
0.8
0.6
20
0.4
10
0.2
0
40 M
20 M
0
0
1000
2000
Time, s
FIGURE 8.11
H
2
S-mediated vasorelaxation. Rat aorta segments suspended in an organ bath containing
the miniature PHSS and equilibrated with 40 µM O
2
are stimulated to constrict with 100 nM phenylephrine
(PE). Subsequent addition of H
2
S causes an immediate relaxation event that gradually recovers as the H
2
S
is oxidized or removed by the gas perfusion stream. Repeated additions of H
2
S at physiologically relevant
concentrations demonstrate a predictable kinetic response.
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