Roles of ANG II and bradykinin in the renal regional blood flow responses to ACE inhibition in sodium-depleted dogs.
The relative contributions of ANG II and bradykinin (BK) to the renal regional blood flow responses during angiotensin-converting enzyme (ACE) inhibition remain unclear. This study was performed to evaluate renal cortical (CBF) and medullary blood flow (MBF) responses to intrarterial administration of enalaprilat (33 microg. kg(-1). min (-1)) after blockade of the ANG II AT(1 )receptors with candesartan (100 microg) in 7 dogs fed a low-salt diet (0.01%) for 5 days. Laser-Doppler flowmetry was used to measure relative changes in CBF and MBF. Candesartan alone increased CBF (+20 +/- 2%) and MBF (+22 +/- 7%). Enalaprilat infusion after candesartan administration resulted in further increases in both CBF (+21 +/- 5%) and MBF (+41 +/- 8%). However, the relative changes in MBF were significantly greater (P < 0.01) than those in CBF. Administration of the BK B(2) receptor blocker icatibant (300 microg) after enalaprilat returned CBF and MBF to values seen with candesartan alone. These data support a substantive role for BK potentiation during ACE inhibitor-induced renal vasodilation in dogs maintained on a low-sodium diet, with a relatively greater effect on MBF compared to CBF.
Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
S A
SA
Omoro
D S
DS
Majid
S S
SS
El Dahr
L G
LG
Navar
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004039:Diet, Sodium-Restricted; D004285:Dogs; D017078:Laser-Doppler Flowmetry; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000172:deficiency*; D013777:Tetrazoles / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; C065679:icatibant; D012964:Sodium; C081643:candesartan; D001920:Bradykinin