INTERACTION BETWEEN CGMP-DEPENDENT DILATORS AND AUTOREGULATION IN RATPREGLOMERULAR VASCULATURE

The influence of guanosine 3',5'-cyclic monophosphate (cGMP)-dependent dilators on autoregulatory responses (AR) of arcuate arteries (ArcA) and afferent arterioles at early sites and at juxtaglomerular sites (J AA) was assessed by videomicroscopy using in vitro blood-perfused juxt amedullary nephron preparations. AR were quantified as fractional chan ges in luminal diameter induced by doubling blood perfusion pressure ( 60-120 mmHg). Baseline AR ranged from 17 +/- 2% to 21 +/- 2% in ArcA a nd from 24 +/- 2% to 34 +/- 4% in JAA. Direct perivascular application s of increasing concentrations of 8-bromo-cGMP (8-BrcGMP, 10 mu M to 1 mM), of the NO donors sodium nitroprusside (10 mu M to 1 mM) and 3-mo rpholino-sydnonimine chlorhydrate (SIN1; 10 mu M to 1 mM), and of rat atrial natriuretic factor (ANF, 0.1 nM to 10 nM) dose- and pressure-de pendently dilated all vessels at 60 mmHg. Concomitantly, AR values wer e dose-dependently reduced or reversed to pressure-induced dilations. During application of 8-BrcGMP and NO donors, the segmental gradient o f sensitivity of AR was ArcA > JAA; the opposite gradient was found wi th ANF (i.e., JAA > ArcA). The present results demonstrate that compou nds known to utilize the cGMP-signaling pathway act as modulators of A R along the juxtamedullary preglomerular vasculature.