Acquired tolerance to dilator action of hydrallazine during oral administration

1 The effect on forearm blood flow of local intra-arterial infusion of hydrallazine has been studied in twelve patients with essential hypertension and six normal subjects. 2 When the patients with hypertension were not taking hydrallazine by mouth, they responded to intra-arterial infusions with a dose-dependent increase in forearm blood flow that was not significantly different from that in normal subjects. 3 When the patients were taking hydrallazine by mouth, the increase in forearm flow in response to intra-arterial infusions was reduced and forearm vascular resistance did not fall as low as it did in the control study (P less than 0.01). 4 In four patients, the response to intra-arterial hydrallazine was attenuated to a major extent, and in three of these, there was little or no response to oral treatment. In eight patients, the response to intra-arterial hydrallazine did not fall below one half of that in the control study and this minor reduction in sensitivity might be expected to impair, but not abolish, the response to oral treatment. 5 It is concluded that the resistance vessels commonly develop tolerance to the dilator action of hydrallazine during long-term oral therapy. In some patients a high degree of tolerance develops and this is an important cause of failure to respond to oral treatment.