Direct effects of dopamine on colonic mucosal pH: implications for tonometry.
Tonometric measurements of colonic and gastric mucosa pH are used as indirect determinants of splanchnic perfusion in shocked patients or those undergoing aortic cross-clamp. Mucosal acidification in response to splanchnic vasodilators such as dopamine has been assumed to signify ischemia. However, cellular acidification may occur independent of oxygenation and the direct effects of dopamine on mucosal acid-base are unknown. We examined the effects of dopamine on cellular pH (independent of oxygenation) of intestinal mucosa in vitro. Crypts isolated from the distal colon of Sprague-Dawley rats were loaded with a pH-sensitive fluorescent probe, perfused with a Hepes-buffered Ringers solution, and imaged with confocal laser scanning microscopy. In separate experiments, crypts were loaded with a calcium-sensitive probe (Fura-2) and concentrations of free cytosolic calcium were measured with fluorescence imaging. Dopamine perfusion produced a reversible cytosolic acidification of crypts which was not significantly affected by (i) the nominal absence of bicarbonate, (ii) alpha- and beta-adrenergic receptor blockade, or (iii) protein kinase C inhibition. Dopamine did not significantly affect intracellular calcium concentrations. However, dopamine-induced acidification was inhibited by (a) blocking sodium-hydrogen exchange with amiloride, (b) prior exposure to adenosine 3', 5'-cyclic monophosphate (cAMP), or (c) protein kinase A blockade (all P < 0.01). Dopamine directly acidifies mucosal crypt cells in a mechanism that involves a cAMP-mediated inhibition of sodium-hydrogen exchange. This finding accounts for the acidification of intestinal mucosa during low-dose dopamine infusion despite a demonstrable improvement in splanchnic perfusion. Direct mucosal effects of pharmacological agents must be considered in the evaluation of perfusion parameters based on tonometric data.
Winter
D C
DC
Department of Surgery, Yale University, New Haven, Connecticut 06510-8026, USA.
O'sullivan
G C
GC
Harvey
B J
BJ
Geibel
J P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D003600:Cytosol / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D018613:Microscopy, Confocal; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors
D005456:Fluorescent Dyes; D017923:Sodium-Hydrogen Exchangers; D011494:Protein Kinases; D002118:Calcium; D016257:Fura-2; D004298:Dopamine