Several vasodilators exert their effect by bindng to G-protein linked endothelial receptors, an action which increases [Ca]ic, thus stimulating ecNOS, generating NO and causing vasodilation. IR might alter this process at one or more of these steps, altering the net effect of these agents on vascular homeostasis. We determined the effects of IR on bradykinin (BK), thrombin (TT) and ADP, all receptor and NO-dependent agents. Mesenteric artery was removed from 3- and 35-day old swine, either controls (C) or animals subjected to IR in vivo, achieved by lowering mesenteric flow 90% for 1h followed by reperfusion for 2h. Rings were mounted in vitro for tension recording; one agent per ring was given after phenylephrine precontraction. Data shown in the table are expressed as p50, ie.,the agonist concentration which produced 50% relaxation. Statistical symbols: *p<.01 v C; #p<.01 v 3-d. Note that I/R decreased the p50 for BK, but increased the p50 for ADP, the latter only in 3-day old rings. Other rings were administered NaF, which directly activates G-proteins in an “all-or-none” manner. Rings from 3- and 35-d control subjects demonstrated 95% dilation in response to 7 μmol NaF. I/R rings from 35-, but not 3-day old subjects, demonstrated dilation in response to 3 μmol NaF, a significant difference(p<.01). This observation may suggest that the G-protein transduction mechanism is upregulated post-I/R, but only in older rings. Conclusions: i) The effect of BK, but not ADP or TT, is age-dependent under control conditions; ii) the effect of I/R on these responses is age- and agent-dependent. Perhaps of greatest interest is that the threshold for direct G-protein stimulation significantly decreased post-I/R in an age-dependent manner. Speculation: We have previously shown that I/R exerts an age-dependent effect on intestinal vascular regulation. This observation may, in part, be explained by the age- and agent-dependent effect of I/R on the response to NO-dependent agonists, especially ADP. This circumstance may be important in the pathogenesis of post-I/R intestinal ischemia.

Table 1 No caption available.
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