Role of H+ and alpha 2-receptors in escape from sympathetic vasoconstriction

In a previous study, we noted that mesenteric venous pH falls during the reductions in intestinal blood flow caused by sympathetic stimulation and that alpha 2-receptor antagonists enhanced autoregulatory escape (the partial recovery that blood flow undergoes despite sustained sympathetic stimulation). In addition, other studies indicated that increased [H+] selectively inhibits the responsiveness of postjunctional alpha 2-receptors to norepinephrine (NE). Therefore, we investigated the role of H+ in escape by 1) measuring the rate of unbuffered H+ release during sympathetic stimulation in isolated loops of canine small bowel, 2) infusing acidic buffer intra-arterially and determining the effects of acidosis on sympathetic vasoconstriction and escape, 3) ascertaining the effects of acidosis on the release rate of endogenous NE during sympathetic stimulation, and 4) determining whether acidosis exerts effects in vivo on post-junctional responses to the selective alpha 1- and alpha 2-agonists, phenylephrine and clonidine, respectively. Our findings were that 1) the rate at which the gut released H+ into blood increased during sympathetic stimulation, 2) infusing acidic buffer to lower venous pH from 7.3 to 7.1 attenuated the initial vasoconstrictor response after 30 s of stimulation, 3) acidosis caused blood flow to return further toward control despite continued stimulation and thus enhanced escape, 4) acidosis did not impair NE release at either 30 s or 6 min of stimulation, and 5) acidosis inhibited the intestinal vasoconstrictor effects of selective alpha 2- but not alpha 1-agonists. The results support the hypothesis that escape from sympathetic vasoconstriction occurs, in part, because increased [H+] inhibits alpha 2-mediated postjunctional responses to neuronally released NE.