Reninlike enzymatic activity in the cerebral microvessels of the rat

Extrarenal renin has been a subject of considerable interest. Chiefly, studies have focused on brain and vascular renin activity in large arteries. A method now exists for the isolation from the cerebrum of microvascular tissues consisting of arterioles, capillaries and venules. The present study has demonstrated reninlike enzymatic activity within the cerebral microvasculature of the rat that is distinct from plasma renin activity. Maximal activity was observed at pH 4.5 with no measurable activity at pH 7.4. Activity with homologous renin substrate was only 13% of that measured with hog substrate whereas a 400-fold increase in reninlike specific activity was observed when microvessel homogenates were incubated with synthetic tetradecapeptide renin substrate. Bilateral nephrectomy did not affect microvascular reninlike activity. Pepstatin 15 nM, abolished reninlike activity in microvessel homogenates. Mean specific microvessel reninlike activity was 1.15 +/- 0.20 pg angiotensin I . microgram protein-1 . h-1 in control animals. Neither sodium depletion nor DOC-saline administrations caused a significant change in microvascular reninlike activity. It is suggested that the reninlike activity observed in microvessels is an acid protease, perhaps cathepsin D derived from lysosomes.