Verapamil abolishes the preglomerular response to ANG II during intrarenal nitric oxide synthesis inhibition.
We have recently reported that intrarenal nitric oxide (NO) synthesis inhibition exaggerates the preglomerular vasoconstrictor response more than the postglomerular response to angiotensin II (ANG II) in dogs. Previous studies have suggested that preglomerular vasoconstriction may be more dependent on extracellular calcium than postglomerular vasoconstriction. The purpose of this study is to determine whether the enhanced preglomerular response to ANG II during intrarenal NO synthesis inhibition occurs through voltage-gated calcium channels. In three groups of anesthetized dogs with stop-flow kidneys, the renal hemodynamic response to intrarenal ANG II infusion (2.0 ng.kg-1.min-1) was determined. Renal artery pressure was servo-controlled at 80 +/- 1 mmHg, and glomerular filtration rate was zero. In vehicle-treated dogs, ANG II decreased renal blood flow (RBF) by 29% and increased glomerular hydrostatic pressure (Pg) by 2.7 +/- 1.9 mmHg. Postglomerular vascular resistance increased by 51%, whereas preglomerular resistance was unchanged in response to ANG II. In dogs pretreated with an intrarenal infusion of NG-nitro-L-arginine methyl ester (L-NAME; 5 micrograms.kg-1.min-1) for 60 min, ANG II decreased RBF by 36% and decreased Pg 4.4 +/- 2.9 mmHg. In contrast to the vehicle-treated group, preglomerular resistance increased by 261% and postglomerular resistance increased by 48% after ANG II infusion in the L-NAME-treated group. In dogs pretreated with an intrarenal infusion of L-NAME and verapamil (50 micrograms/min) for 60 min, the renal hemodynamic response to ANG II was similar to the response in the vehicle-treated dogs. ANG II decreased RBF by 25% and decreased Pg by 5.3 +/- 1.2 mmHg. Postglomerular resistance increased by 51%, whereas preglomerular resistance was unchanged in response to ANG II infusion in dogs with intrarenal NO synthesis and voltage-gated calcium channel blockade. These data indicate that the preglomerular response to ANG II under conditions of reduced NO synthesis within the kidney is dependent on voltage-gated calcium channels.
Schnackenberg
C G
CG
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Granger
J P
JP
D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D007678:Kidney Glomerulus / Q000098:blood supply / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow; D014655:Vascular Resistance / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D009569:Nitric Oxide; D002216:Captopril; D014700:Verapamil; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester