Impairment of endothelium-dependent relaxations may be of primary importance in hypertension, if this impairment were to occur in resistance arteries. Therefore, endothelium-dependent relaxations to acetylcholine were studied in the mesenteric resistance vessels of spontaneously hypertensive and Wistar-Kyoto rats. Rings with and without endothelium were suspended in a myograph filled with physiological salt solution at 37 degrees C and aerated with 95% O2/5% CO2; the isometric tension was recorded. Acetylcholine caused relaxations only in rings with endothelium. In the spontaneously hypertensive rat, relaxations were impaired and markedly biphasic with an early rapid relaxation followed by a secondary contraction. Indomethacin inhibited the secondary response and augmented the duration of the relaxations induced by acetylcholine in the arteries from spontaneously hypertensive rats. These findings suggest that the decreased endothelium-dependent relaxation to acetylcholine in mesenteric resistance vessels of the spontaneously hypertensive rat is due to the release of a constrictor prostanoid which partly offsets the response of the vascular smooth muscle to endothelium-derived relaxing factor(s).