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.

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