title: Suppression of blood flow autoregulation plateau during nitric oxide blockade in canine kidney.
abstract: We examined the autoregulation of renal blood flow (RBF) and renal function in anesthetized dogs during nitro-L-arginine (NLA)-induced blockade of endothelium-derived nitric oxide (EDNO). Intrarenal infusion of NLA (50 micrograms.kg-1.min-1) increased systemic arterial pressure (AP) and renal vascular resistance (RVR). RBF decreased by 27 +/- 3%, but glomerular filtration rate remained unchanged. There were reductions in urine flow (24 +/- 5%), urinary sodium excretion (42 +/- 10%), and fractional excretion of sodium (40 +/- 11%). The vasodilatory responses to intrarenal injections of ATP (1, 5, 10 microM) were reversed, whereas such responses to doses (10, 50, 100 ng) of acetylcholine (ACh) were attenuated during NLA infusion. Indomethacin (5 mg/kg iv) treatment further reduced but did not completely abolish ACh-induced vasodilation, suggesting that factor(s) other than EDNO and prostaglandins may also mediate ACh-induced vasodilation in the kidney. Although there was a suppression of the plateau of the AP-RBF relationship with a rightward shift in the slope of the linear portion of the curve during EDNO blockade, the normal autoregulatory pattern remained intact. Similar responses were seen in dogs treated with the angiotensin-converting enzyme inhibitor, MK-422. These data indicate that EDNO contributes to the normally low renal vascular tone by influencing an autoregulation-independent component of RVR. However, the basic capability to adjust RVR (autoregulation-responsive component) in response to changes in AP is essentially autonomous from EDNO activity.
authors.affiliation: Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
authors.forename: D S
authors.initials: DS
authors.lastname: Majid
authors.forename: L G
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood
chemical_list: D019335:Nitroarginine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001120:Arginine; D012083:Renin; D000109:Acetylcholine