EFFECTS IN THE WHOLE ANIMAL 515 



indicate that the sympathetic catecholamines are not primarily involved. 

 Although quinones can oxidatively deaminate certain amines in vitro, it 

 is very unlikely that this reaction occurs in vivo, and indeed there is evi- 

 dence that the quinones can interfere with the normal enzymic metabolism 

 of amines. Beyer (1946), on the basis of unpublished clinical results by 

 others, and the failure to find an antihypertensive action in species other 

 than the rat — e. g., Goldblatt could observe no blood pressure lowering 

 in hypertensive dogs — concluded that the hypotensive action in rats is 

 a special case and is probably not related to the destruction of amines. 

 This pronouncement seems to have terminated study in this field and the 

 clinical value of sucfi quinones has not been adequately determined, nor 

 has the mechanism of the hypotensive action been elucidated. Although 

 it would be very optimistic to believe that the ordinary quinones might 

 be of clinical value in hypertension, it might be worthwhile to investigate 

 the effects of the quinones on formation, release, action, and metabolism 

 of angiotensin. 



Actions on the Blood and Hematopoietic System 



The in vivo formation of methemoglobin has been observed in dogs given 

 2)-benzohydroquinone (Gibbs and Hare, 1890), catechol (Heubner, 1913), 

 menadione, and menadiol (Cannava, 1948 a, b); in rabbits given p-benzo- 

 quinone (Ellinger, 1923) and menadione (Fromherz, 1941); in rats given 

 p-benzohydroquinone (Ellinger, 1923); and in cats given ^^-benzohydro- 

 quinone (Jung and Witt, 1947). The amount of methemoglobin present in 

 the blood is never very high, even following toxic doses of the quinones, 

 and is usually only in trace quantities. The levels may occasionally fall 

 after an initial rise. Thus it seems quite clear that neither the acute nor 

 chronic toxic actions of the quinones are due to the elevation of methemo- 

 globin levels, although combined with other actions leading to a reduction 

 in erythrocytes and hemoglobin it might contribute slightly. The formation 

 of methemoglobin in vitro when blood is incubated with p-benzoquinone 

 was demonstrated by Heubner (1913). No methemoglobin is produced by 

 p-benzohydroquinone anaerobically, but upon admission of oxygen the 

 sequence Hb -> HbOg -^ met-Hb was observed. That this is a simple direct 

 oxidation of hemoglobin is indicated by the fact that the reaction occurs 

 when crystalline horse hemoglobin is mixed with j^-benzoquinone. Never- 

 theless, Heubner found very little methemoglobin formed in dogs injected 

 with p-benzohydroquinone or catechol. Oettel (1936) claimed that the 

 lack of a marked in vivo action is due to the fact that the blood contains 

 substances maintaining the hydroquinone in a reduced form and, in a 

 series of experiments involving acute and chronic administration of p-ben- 

 zohydroquinone to several species, found little or no methemoglobin in the 

 blood, even at the time of death, although methemoglobin formed more 



