Short- and long-term determinants of cardiovascular function and therapy: contributions of circulating and tissue renin-angiotensin systems.

Cardiovascular function is regulated by short-term and long-term neurohormonal and autocrine-paracrine mechanisms that act synergistically or sequentially. Structural adaptive changes that occur progressively over time also contribute to the long-term outcome. The renin-angiotensin system (RAS) can operate as both an endocrine and an autocrine-paracrine (tissue) system. The endocrine component is involved with acute circulatory homeostasis, whereas the tissue RAS, we believe, participates in the tonic regulation of cardiovascular function and structure. Angiotensin converting enzyme (ACE) inhibitors exert both acute and long-term effects on blood pressure. The acute response is influenced by the activity of the endocrine RAS. On the other hand, the chronic response to ACE inhibition is determined by both serum and tissue effects. The reversal of hypertensive cardiovascular structural changes as well as the enhancement of renal sodium excretion by ACE inhibitors are important mechanisms of their long-term antihypertensive action.