Cardiovascular-renal responses to long-term nitric oxide inhibition during angiotensin II-AT1 receptor inhibition.
A previous study in conscious dogs showed that the normal hypertensive response to short-term nitric oxide synthesis inhibition was markedly attenuated during angiotensin II-AT1 receptor inhibition. However, whether angiotensin plays an important cardiovascular role in the dog during long-term nitric oxide synthesis inhibition has not been determined and was therefore the goal of this investigation. Studies were conducted in 16 conscious dogs that received angiotensin AT1 receptor inhibition with L158809 (N = 8) or vehicle (N = 8) for 12 d. During the last 6 d of this infusion, nitric oxide synthesis was inhibited by infusing NG-nitro-L-arginine methyl ester intravenously at 37.1 nmol/kg/min. In both the AT1 and vehicle groups, nitroarginine infusion significantly decreased the acetylcholine depressor response, glomerular filtration rate, renal plasma flow, and heart rate, and increased arterial pressure and renal vascular resistance in a similar manner, whereas it caused little change in the urinary excretion of sodium and water or in plasma renin activity. In conclusion, the long-term responses of arterial pressure, renal hemodynamics, and the renal excretion of sodium and water to nitric oxide synthesis inhibition were not significantly influenced by blockade of angiotensin AT1 receptors with L158809 in the dog.
Manning
R D
RD
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Hu
L
L
D000109:Acetylcholine / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006728:Hormones / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D006728:Hormones; D007093:Imidazoles; D013777:Tetrazoles; D009569:Nitric Oxide; C070967:L 158809; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester