Do intravenous and subcutaneous angiotensin II increase blood pressure by different mechanisms?

1. Angiotensin (Ang) II plays a key role in blood pressure regulation. Mechanisms of the pressor effect of chronic intravenous AngII administration include vasoconstriction, stimulation of the sympathetic nervous system and aldosterone production, as well as direct effects on renal excretion of sodium and water. 2. Chronic AngII administration by subcutaneous minipump at doses higher than required to increase blood pressure by the intravenous route has identified additional pressor mechanisms, including the immune system, cytokines and matrix metalloproteinases. However, pressor doses of subcutaneous AngII may exceed the angiotensinogen synthesis rate and produce inflammation, fibrosis and necrosis of skin overlying the minipump. 3. Evidence that chronic subcutaneous and intravenous AngII increase blood pressure by different mechanisms includes the prevention of the pressor effects of subcutaneous, but not intravenous, AngII by angiotensin-converting enzyme inhibition. Furthermore, low doses of subcutaneous AngII reduce blood pressure of female, but not male, rodents and higher doses are less pressor in females than in males, whereas intravenous AngII is equally pressor in males and females. 4. Pressor doses of chronic subcutaneous AngII produce greater weight loss, anorexia and reduced kidney weight and cause greater vascular, cardiac and renal pathology than equally pressor doses of chronic intravenous AngII. 5. The different effects of chronic intravenous and subcutaneous AngII suggest that these two models of hypertension give different information and may differ in their relevance to blood pressure regulation in physiological and pathological states such as hypertension in humans.