Renal and circulatory effects of medullipin I, as studied in the in-vivo cross-circulated isolated kidney and intact Wistar-Kyoto (WKY) rat.

The renal medulla harbours powerful humoral antihypertensive mechanisms, as earlier explored in unclipping experiments on renal hypertensive rats or in normotensive isolated kidneys cross-circulated at increased perfusion pressures from 'donor rats', in which renal function also seemed to be affected. Injection of the renomedullary factor medullipin I (Med I; formerly ANRL) mimics these haemodynamic responses, and Med I seems to be one of the most important mediators of the depressor effects. The present study was performed to analyse further the haemodynamic and, particularly, the renal effects of Med I, using anaesthetized intact WKY rats and constant-pressure perfused (90 mmHg) isolated WKY kidneys, cross-circulated by these intact 'donor' rats. Mean arterial pressure (MAP), heart rate (HR) and renal function were followed for one 30-min period before and two 30-min periods after injection of 1 mg Med I (M; n = 7) or an equal volume of saline as control (C; n = 13). In the intact 'donor' WKY, MAP and HR remained largely constant in C during the three periods, being 126 +/- 5, 125 +/- 5, and 120 +/- 5 mmHg, while MAP fell in the M group after Med I, from 121 +/- 5 to 107 +/- 7 and 107 +/- 5 mmHg (P less than 0.05), and also HR tended to decrease in M. Renal resistance (RR) fell while renal plasma flow (RPF) and glomerular filtration rate (GFR) increased significantly (P less than 0.05) after Med I in the M donor rats despite their MAP reduction. However, in the constant-pressure perfused, cross-circulated kidneys the RR, RPF and GFR changes were clearly more pronounced (P less than 0.01) and also diuresis, natriuresis, osmolar excretion and osmolar clearance increased significantly after Med I (P less than 0.01). In conclusion, the present results support the view that Med I not only has important and long-lasting depressor effects but also affects renal function in important ways, inducing vasodilatation and increasing GFR, RPF, diuresis and sodium-osmolar excretion.