1 This study has administered pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) or amiloride to attenuate the remodelling and associated functional changes, especially an increased cardiac stiness, in DOCA-salt hypertensive rats. body wt) without lowering systolic blood pressure. 4 Collagen deposition was signi®cantly increased in the interstitium after 2 weeks and further increased with scarring of the left ventricle after 4 weeks; pirfenidone and amiloride reversed the increases and prevented further increases. This accumulation of collagen was accompanied by an increase in diastolic stiness constant; both amiloride and pirfenidone reversed this increase. 5 Noradrenaline potency (positive chronotropy) was decreased in right atria (neg log EC50: control 6.92+0.06; DOCA-salt 6.64+0.08); pirfenidone but not amiloride reversed this change. Noradrenaline was a more potent vasoconstrictor in thoracic aortic rings (neg log EC50: control 6.91+0.10; DOCA-salt 7.90+0.07); pirfenidone treatment did not change noradrenaline potency. 6 Thus, pirfenidone and amiloride reverse and prevent cardiac remodelling and the increased cardiac stiness without reversing the increased vascular responses to noradrenaline. British Journal of Pharmacology (2002) 135, 961 ± 968