Direct effects of dopamine on colonic mucosal pH: Implications for tonometry

Tonometric measurements of colonic and gastric mucosa pH are used as indire ct determinants of splanchnic perfusion in shocked patients or those underg oing aortic cross-clamp. Mucosal acidification in response to splanchnic va sodilators 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 oxygenat ion) of intestinal mucosa in vitro, Crypts isolated from the distal colon o f Sprague-Dawley rats were loaded with a pH-sensitive fluorescent probe, pe rfused with a Hepes-buffered Ringers solution, and imaged with confocal las er scanning microscopy, In separate experiments, crypts were loaded with a calcium-sensitive probe (Fura-a) and concentrations of free cytosolic calci um 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 bicarbon ate, (ii) alpha-and beta-adrenergic receptor blockade, or (iii) protein kin ase C inhibition. Dopamine did not significantly affect intracellular calci um concentrations. However, dopamine-induced acidification was inhibited by (a) blocking sodium-hydrogen exchange with amiloride, (b) prior exposure t o adenosine 3', 5'-cyclic monophosphate (cAMP), or (c) protein kinase A blo ckade tall P < 0,01), Dopamine directly acidifies mucosal crypt cells in a mechanism that involve s a cAMP-mediated inhibition of sodium-hydrogen exchange. This finding acco unts for the acidification of intestinal mucosa during low-dose dopamine in fusion despite a demonstrable improvement in splanchnic perfusion. Direct m ucosal effects of pharmacological agents must be considered in the evaluati on of perfusion parameters based on tonometric data. (C) 1999 Academic Pres s.