Localisation and physiological effects of tissue renin-angiotensin systems

Evidence suggests that the tissue renin-angiotensin-aldosterone (RAA) systems play an important role in BP homeostasis, with the possible importance of the vascular RAA system in hypertension being of particular interest. Although angiotensin II has a direct vasoconstrictor action, local production of angiotensin II may also be important in the control of sympathetic neurotransmission and in smooth muscle hyperplasia. Whilst renin-like activity can be demonstrated in arterial walls, the source of this is still uncertain. Uptake of renally derived plasma renin can be demonstrated, but local synthesis of biologically significant quantities of renin cannot be excluded by conventional assay methods. Recent studies of renin gene expression demonstrate the presence of renin mRNA in the arterial wall, liver, adrenal gland, heart and brain. The reduction of BP by ACE inhibitors, even when plasma renin activity is not elevated, has not been explained by an action on a local system and previous research efforts have focused on demonstrating renin-like activity in extra-renal tissues. However it is now possible to study those control systems which regulate the extra-renal RAA system. We have demonstrated a qualitative difference between plasma renin taken up by the arterial wall and renin gene expression (as an indicator of local renin synthesis). Unlike circulating renin, local extra-renal renin gene expression is not influenced by sodium balance or by feedback inhibition as a result of high renin levels. Locally generated angiotensin II derived from locally synthesised renin may therefore perform a different function from that of the circulating RAA system in vascular control.(ABSTRACT TRUNCATED AT 250 WORDS)