The myogenic response is a process by which blood vessels autoregulate vascular smooth muscle tone in response to changes in transmural pressure. It is characterized by vessel contraction or dilation with increased or decreased pressure, respectively. We sought to identify whether acidosis impacts the myogenic response in rat coronary resistance arteries. Ventricular septal arteries were isolated from male Sprague-Dawley rats and mounted on a pressure myograph. The myogenic response was assessed by measuring the arterial diameter at pressures of 10-120 mm Hg. The fluorescence indicators 2',7'-bis-(carboxyethyl)-5(and-6)-carboxyfluorescein and Fura-2 were utilized to measure intracellular pH (pH(i)) and intracellular free calcium concentration ([Ca(2+)](i)), respectively. A decrease in the extracellular pH (pH(o)) from 7.4 to 6.9 produced a fall in pH(i) and an increase in the myogenic response. Under nominally HCO (3) (-) /CO(2)-free conditions at a constant pH(o), blockade of the sodium-hydrogen exchanger with HOE694 also resulted in a fall in pH(i) and a similar enhancement of myogenic activity. Concentration response curves were constructed to measure the potencies of the HOE694 effects: the EC(50) was 34 microM for the pH(i) change and 19 microM for vessel constriction. Apparent [Ca(2+)](i) remained unchanged during HOE694-induced intracellular acidification. Furthermore, in the presence of HCO (3) (-) , HOE694 did not markedly affect pH(i) and vascular tone remained unaltered. Our data demonstrate that acidosis augments myogenic constriction of rat coronary arteries. These effects are due to a fall in pH(i) consequent upon the reduction in pH(o) and may reflect an increased myofilament [Ca(2+)](i) sensitivity within vascular smooth muscle cells.