Interaction between cGMP-dependent dilators and autoregulation in rat preglomerular 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 (JAA) was assessed by videomicroscopy using in vitro blood-perfused juxtamedullary nephron preparations. AR were quantified as fractional changes in luminal diameter induced by doubling blood perfusion pressure (60-120 mmHg). Baseline AR ranged from 17 +/- 2% to 21 +/- 2% in ArcA and from 24 +/- 2% to 34 +/- 4% in JAA. Direct perivascular applications of increasing concentrations of 8-bromo-cGMP (8-BrcGMP, 10 microM to 1 mM), of the NO donors sodium nitroprusside (10 microM to 1 mM) and 3-morpholino-sydnonimine chlorhydrate (SIN1; 10 microM to 1 mM), and of rat atrial natriuretic factor (ANF, 0.1 nM to 10 nM) dose- and pressure-dependently dilated all vessels at 60 mmHg. Concomitantly, AR values were dose-dependently reduced or reversed to pressure-induced dilations. During application of 8-BrcGMP and NO donors, the segmental gradient of sensitivity of AR was ArcA > JAA; the opposite gradient was found with ANF (i.e., JAA > ArcA). The present results demonstrate that compounds known to utilize the cGMP-signaling pathway act as modulators of AR along the juxtamedullary preglomerular vasculature.
Bouriquet
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Groupe Rein et Hypertension, Hôpital St. Charles, Montpellier, France.
Casellas
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D
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000098:blood supply*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009599:Nitroprusside; C016276:8-bromocyclic GMP; C002385:linsidomine; D009320:Atrial Natriuretic Factor; D008981:Molsidomine; D006152:Cyclic GMP