Myogenic constriction in renal failure - cause and therapy

PhD ceremony: Mr. P. Vavrinec, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Myogenic constriction in renal failure - cause and therapy

Promotor(s): prof. R.H. Henning

Faculty: Medical Sciences

In resistance arteries, myogenic constriction (MC) is activated by elevated transmural pressure, which causes contraction of arterial smooth muscle leading to reduction of vessel lumen thereby reducing blood flow in target organs. Myogenic constriction, as a vascular autoregulatory mechanism, helps to maintain stable blood flow over a wide systemic pressure range. Failure of MC in preglomerular arteries causes increased glomerular pressure resulting in chronic kidney disease (CKD). Many factors may contribute to impairment of MC e.g. hypertension or diabetes mellitus. Peripheral arteries MC is, however, affected as well. We found that higher MC of preglomerular vessels is associated with lower vulnerability to damage of kidneys in several rat models: reduced renal mass/hypertension – 5/6Nx, type 2 diabetes mellitus – ZDF rat, and in ageing induced hypertension with predisposition to kidney damage – FH rat. Furthermore, we examined MC of mesenteric artery, as a representative of the peripheral vasculature, in these models and demonstrate that development of hypertension - but not CKD - is associated with decreased MC in this artery. Then we identified in vivo glomerular vascular contractility to Angiotensin II can predict individual susceptibility to CKD in the adriamycine model and in 5/6Nx model. Finally we showed that several types of treatment improve MC in both the renal and peripheral vascular bed of rats with CKD with and without hypertension. The studies presented in this thesis therefore demonstrate that the patency of vascular smooth muscle contraction in small renal arteries is pivotal in limiting renal damage and limiting progression of renal disease.