Biomedical subjects

A B Fogo

Publications and source records attributed to A B Fogo.

39 records · Page 3Linked to original sources

PubMedDate not supplied

New insights into the renin-angiotensin system and hypertensive renal disease.

The role of the renin-angiotensin system in hypertension and end organ damage has long been recognized. Recent advances in genetic models and newly available pharmacologic tools have allowed dissection of the mechanisms of actions of the renin-angiotensin system in hypertensive kidney disease. The newly cloned AT(2) receptor is now recognized to oppose many of the AT(1) receptor"s actions. The renin-angiotensin system is now recognized to be linked to induction of plasminogen activator inhibitor-1 (PAI-1), possibly via the AT(4) receptor, thus promoting both thrombosis and fibrosis. Interactions of the renin-angiotensin system with aldosterone and bradykinin may have impact on both blood pressure and tissue injury. The effects of angiotensin 1 converting enzyme inhibitors versus those of the newly available AT(1) receptor antagonists on blood pressure and organ damage are undergoing evaluation in clinical trials. Finally, polymorphisms of genes relevant to the renin-angiotensin system appear to affect response to treatment, although this effect varies in different populations.

Animals↗

PubMedDate not supplied

Mesangial matrix modulation and glomerulosclerosis.

Progressive deterioration of the kidney is common to many renal diseases. The structural injuries which lead to this progressive loss of function consist of focal segmental glomerulosclerosis and tubulointerstitial fibrosis and atrophy. These processes were previously thought to be inexorable, regardless of the primary disease. However, recent observations point to the possibility of reversal of sclerosis. Mesangial matrix accumulation is the cornerstone of glomerulosclerosis and results when matrix synthesis exceeds matrix degradation. The renin-angiotensin system appears to be one central component of this process, with links to numerous mechanisms which promote matrix accumulation. Most recently, direct induction of plasminogen activator inhibitor-1 by angiotensin has been recognized. Plasminogen activator inhibitor-1 not only promotes thrombosis, but also inhibits matrix degradation. The various mechanisms which modulate mesangial matrix accumulation and their potential reversibility are reviewed.

Animals↗

PubMedDate not supplied

Mechanisms in nephrosclerosis and hypertension-beyond hemodynamics.

These studies support that global glomerulosclerosis is a key lesion in human hypertensive nephrosclerosis, and cannot be simply explained by worse vascular sclerosis caused by higher blood pressure. Possible pathogenetic mechanisms include genetic susceptibility, accelerated aging and a primary microvascular disease. The potential importance of the renin angiotensin system in glomerular sclerosis is underscored by the effectiveness of therapies that aim to inhibit its manifold actions, including induction of plasminogen activator inhibitor-1 (PAI-1). Further, regression of existing glomerulosclerosis, including age-related renal and vascular sclerosis, can be achieved in various experimental settings by high dose angiotensin inhibiton, and is linked to inhibition of PAI-1. Ongoing studies will establish which of these provocative findings from animal models are relevant to human diseases, and may lead to optimal therapies to forestall progression and perhaps even induce regression of sclerosis.

Animals↗