Differential effects of clonidine, dopamine, dobutamine, and dopexamine onbasal and acid-stimulated mucosal blood flow in the rat stomach

Objective: To analyze the effects of clonidine, dopamine, dobutamine, and d opexamine on gastric mucosal blood flow (GMBF) at baseline and after stimul ation by acid back diffusion through a disrupted gastric mucosal barrier. Design: Prospective, randomized, unblinded study. Setting: University research laboratory. Subjects: Adult Sprague-Dawley rats. Interventions: Mean arterial blood pressure (MAP) and heart rate (HR) were recorded from a carotid artery of the phenobarbital-anesthetized animals, A jugular vein was cannulated for continuous infusion of saline and intraven ous drug administration. The stomach was prepared for luminal perfusion and for recording GMBF with the hydrogen gas clearance technique. Gastric muco sal vascular conductance (GMVC) was calculated as GMBF divided by MAP, Measurements and Main Results: Clonidine (37.5 and 112.5 nmol.kg(-1)) lower ed MAP and HR and caused gastric vasodilation as shown by a rise of GMVC, T he 2.5-fold increase in GMVC elicited by gastric perfusion with HCl (0.15 M ) plus ethanol (25%) was depressed by clonidine, All cardiovascular effects of clonidine were prevented by the alpha (2)-adrenoceptor antagonist idazo xan (2 mu mol.kg(-1)). Infusion of dopamine (15 and 45 mu mol.kg(-1).hr(-1) ), dobutamine, or dopexamine (each at 5 and 15 mu mol.kg(-1).hr(-1)) caused tachycardia. GMVC at baseline was attenuated by the higher dose of dopamin e and dopexamine, but not dobutamine, In contrast, the acid-induced vasodil ation in the gastric mucosa was depressed by dobutamine and dopexamine, but not dopamine, Conclusions: Clonidine, dobutamine, and dopexamine at high dosage suppress the gastric mucosal vasodilator response to acid back diffusion, which is a n important defense mechanism. Although the dose equivalence between rats a nd humans is not known, the antivasodilator effects highlight an adverse ac tion whereby large doses of dobutamine, dopexamine, and clonidine may compr omise gastric mucosal homeostasis and facilitate stress ulcer formation, Do pamine lacks this detrimental activity.