The renin-angiotensin system and the heart: beyond 2000.

Renin-angiotensin is both a circulatory and a local tissue system. However, in most circumstances, renin present in the heart and blood vessels is taken up from the plasma, and the kidney is the prime source of this renin. Tissues can then modulate and control the production of angiotensin II. In various organs, angiotensin II has local actions. In the heart, working through the AT1 receptor, it increases contractility and may cause cardiocyte hypertrophy. Indirectly, the heart is also very much affected by the vascular actions of angiotensin II. However, the net result on the heart is the product of an important interaction between a large number of factors. There is little doubt that an inappropriately high plasma (and tissue) level of renin, related to sodium balance, is associated with increased left ventricular hypertrophy and cardiovascular complications. The genetic approach will lead to an understanding of genomic risk factors in hypertension and may identify control systems--at present unknown--which will lead to a new approach to the prevention of cardiovascular death. It is, however, unlikely that such a factor will clearly predict an individual's prognosis, but it will, rather, identify groups at risk. Constellations of genomic interactions with multiple environment factors reduce this power. Modification of the response to angiotensin II using present treatment, or interrupting the response at more distal sites, may enable us to achieve the beneficial effects on cardiac hypertrophy without the detrimental effects.