The site of action and the distribution of angiotensin II have been studied in the mouse . A comparison of the ratios of angiotensin 14C and inulin 3H at the time of the pressor effect reveals an extracellular pattern of distribution . Morphological studies were made using angiotensin coupled to exogenous enzymes which can be demonstrated histochemically . Coupling of angiotensin to horseradish peroxidase or cytochrome c, with glutaraldehyde or difluorodinitrodiphenylsulfone (FNPS) as the coupling agent, does not alter the pattern of its vasopressor response or that of its inactivation ; nor are differences present between angiotensin and the angiotensin-enzyme complexes in the stimulation of in vitro tissue preparations . Dissociation of the complexes was shown not to occur in vitro, but the possibility of a serum factor splitting the complexes immediately after intravenous injection cannot be excluded . Since these complexes are localized on the endothelium and not on the smooth muscle at the time of maximum hypertension, the endothelium is proposed as the site of action for angiotensin .

No abstract

The effects of curarizing drugs, anticholinesterases, and musculotropic substances were studied on the phrenic nerve – diaphragm preparation of the hereditarily dystrophic mouse and of the rat treated with N,N-dimethyl-p-phenylenediamine (PPD), a cytotoxic substance producing dystrophic-like lesions. Both species showed an increased resistance to the neuromuscular blocking activity of d-tubocurarine. Gallamine was also less potent in the dystrophic mouse than in its normal littermate. Both species showed an increased sensitivity to the initial stimulant effect of succinylcholine; on the other hand, the depressant effect of succinylcholine was less intense in PPD-treated rats but unaltered in the dystrophic mouse. The response to neostigmine and physostigmine was decreased in the PPD-treated rat but enhanced in the dystrophic mouse. Musculotropic drugs (chlorpromazine, tetrodotoxin, xanthine derivatives, and veratrine) produced similar effects in normal and dystrophic mice. Two hypotheses are suggested to explain these changes in sensitivity in the dystrophic mouse diaphragm: (a) an increased production of an acetylcholine-like material, and (b) an increase in the number of acetylcholine-sensitive sites on the cell membrane. The changes in drug reactivity of the PPD-treated rat are considered to be due to a functional denervation caused by the cytotoxic properties of PPD.

The methoxy analogs of epinephrine, norepinephrine, and dopamine manifest some activity on smooth muscle and blood pressure. Metanephrine is as potent as epinephrine on rabbit aortic strips. The same compounds demonstrate a lesser potency on rabbit duodenum preparation, while 3-methoxy-dopamine produces a slight contraction of the duodenum. Both metanephrine and 3-methoxy-dopamine have 15 to 25 percent of the pressor activity of the original nonmethylated catecholamines. Normetanephrine is 1/600 as active as norepinephrine on the blood pressure of the cat.

%'he irnfluerlce of perfusion pressure on vcntricuhr hbrillatlo~l was studied in the isolated rabbit heart. Su~dderi drops ill perfusion pressure inhibit veritricular fihrillatir~n in n few minutes, whereas a slow dwrenstt. of the pressure tloes not stop the fit)rilI;ltion, but nevertheless reduces the ventricular liri~lg rate. High perfusion pressures facilitate the inductio~m of fil~rillation; low pressures delay the proeiuction of arrl-iythmias and shorten their duration. I t is postulated that this effect of presure is primarily ~i~echa~lical and not strictly depe~~tlent upon cllanges in the corclriary flow or in the ~rlyocarclial te~riperature.