Plasma renin and "prorenin" in essential hypertension during sodium depletion, beta-blockade, and reduced arterial pressure.

An inactive form of renin is activated by incubating human plasma at -5 degrees C. The relative proportions of active renin and this cryoactivatable "prorenin" in plasmas of untreated hypertensive patients varied widely. However, prorenin increased in parallel with active renin after sodium deprivation or diuretic therapy in 36 patients; the increases were similar whether or not blood-pressure fell. In contrast, propranolol administration in 22 patients lowered active renin in all, but it increased prorenin by 98% in 15 in whom systolic pressure fell. In the other 7 blood-pressure did not change, and beta-blockade produced a fall in total renin (active renin plus prorenin) while prorenin was unchanged. For all 22 there was an inverse relationship between propranolol-induced changes in plasma-prorenin and systolic pressure (r=-0-77, P less than 0-001). The fraction of active plasma-renin fell during propranolol administration from 43% to 18%, regardless of the blood-pressure response. Clonidine produced similar changes in 10 patients. Thus, sodium depletion stimulates total renin release, while propranolol and clonidine produce divergent responses of active renin and prorenin, the changes in prorenin depending on the changes induced in blood-pressure. These observations suggest that propranolol may block intrarenal conversion of prorenin to active renin while also suppressing total renin release. But the latter effect may be offset by concurrent baroreceptor-mediated release of total renin (mostly prorenin) when blood-pressure is lowered.