Effects of Angiotensin II and Some Analogues on Vascular Permeability in the Rabbit

Abstract

Recent investigations in the rat have shown that endothelial cell contraction should be included among the multiple actions of angiotensin II (AII) in large arteries. In the current study, after intravenous injections (60 mg/kg) of the azo dye Evans blue, a segment of the rabbit abdominal aorta was isolated between temporary ligatures and injected with 1 x 10 -10 g of AII diluted in Ringer's solution. Diffuse increased permeability of the aortic endothelium occurred within 60 seconds only in areas exposed to AII. Although injections of Ringer's solution alone produced no blueing, surface staining and scanning electron microscopy of the aortic endothelium after AII administration showed endothelial cell contraction, widening of the interendothelial junctions, and surface sudanophilia. Similar studies were carried out to determine changes in dermal vascular permeability. Of all the substances tested, AII, prostaglandin E 1 (1 x 10 -10 -1 x 10 -8 g), and serum triglycerides (1 x 10 -6 g) produced the most marked vascular response characterized by the appearance, within 15 minutes, of a bluish wheal or papule. Injections of angiotensin I or norepinephrine at concentrations of 10-100 x 10 -9 g or of Ringer's solution alone did not induce skin changes. Synthetic peptides, competitive antagonists to the myotropic and vasopressor activities of AII, blocked extravasation of Evans blue dye injected simultaneously with the octapeptide, but antihistaminics did not inhibit its effects. We concluded that the multiple actions of AII in blood vessels are related not only to the control of blood pressure but also to the regulation of the permeability and the function of the vascular wall as a whole.