Evidence for cardiovascular effects of prorenin.

This report investigates whether there is evidence that prorenin has cardiovascular effects. The report concludes that prorenin may indeed have cardiovascular effects, causing regional vasodilation by counteracting the vasoconstrictor effect of renin, and thereby maintaining blood flow to vital organs. This view is based on several observations. In direct contrast to renin, high levels of prorenin are not associated with vasoconstriction. (1) Prorenin is expressed almost exclusively in tissues with extraordinarily high levels of blood flow: pregnant uterus, placenta, ovaries, kidneys, eyes. (2) In the ovaries, the higher the prorenin level the higher the level of steroid biosynthesis, consistent with a increased tissue perfusion or metabolism. (3) Blood pressure gradually falls when prorenin is infused into monkeys, even when the source of prorenin is contaminated with renin which should increase blood pressure. (4) Prorenin levels positively correlate with renal blood flow under several experimental conditions. (5) Salt sensitivity of blood pressure, a renal vasoconstricted state, is associated with subnormal prorenin levels. (6) Diabetes mellitus and pregnancy, two vasodilated states, are associated with high plasma prorenin levels. (7) Prorenin binds to a membrane receptor that also recognizes renin. Thus, prorenin could vasodilate by competing with the specific uptake of renin and thereby reduce the level of regional vasoconstriction. Altogether, the cardiovascular haemodynamic setting associated with high levels of prorenin is the opposite of that associated with high levels of renin and is consistent with a vasodilator effect in the kidneys and reproductive organs and perhaps elsewhere.