title: Chronic renal failure leads to reduced flow-dependent dilation in isolated rat skeletal muscle arterioles due to lack of NO mediation.
abstract: BACKGROUND
  Chronic renal failure (CRF) is frequently accompanied by systemic vascular alterations which further increase the morbidity and mortality of these patients. However, the nature and the underlying mechanisms of vascular dysfunction are not completely understood. We hypothesized that--in addition to other factors--CRF alters local vasomotor mechanisms that are intrinsic to the vascular wall.
  
  
  METHODS
  Changes in the diameter of isolated, pressurized (at 80 mm Hg) gracilis skeletal muscle arterioles (diameter approximately 150 microm) of female Wistar rats were investigated by videomicroscopy. Arteriolar responses to an increase in flow and vasoactive agents in partially nephrectomized (NX) and sham-operated (control) rats were compared.
  
  
  RESULTS
  In NX rats, serum creatinine and urine protein excretion were increased. Compared to controls, increases in intraluminal flow (from 0 to 40 microl/min) resulted in significantly reduced dilation in arterioles of NX rats (maximum: 32 +/- 4 vs. 15 +/- 4 microm, p < 0.05). Inhibition of nitric oxide (NO) synthesis with L-NAME reduced the dilation of control arterioles but did not affect responses of NX arterioles. Also, dilations in response to histamine were significantly reduced in arterioles from NX rats as compared to control rats. L-NAME significantly decreased histamine-induced dilations of control arterioles, but it did not affect responses of NX arterioles. Dilations in response to the NO donor sodium nitroprusside were also significantly decreased in NX arterioles as compared to responses of control vessels, whereas responses to adenosine and norepinephrine were not significantly different in the two groups.
  
  
  CONCLUSIONS
  We conclude that in rat skeletal muscle arterioles, CRF induced by renal mass reduction alters the mechanosensitive and agonist-induced responses of peripheral arterioles, in part by interfering with NO-signaling mechanisms. These alterations could contribute to increased peripheral vascular resistance and further aggravate the cardiovascular complications in CRF.
authors.affiliation: Department of Pathophysiology, Semmelweis University, Budapest, Hungary. kolako@net.sote.hu
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bagi
authors.forename: Peter
authors.initials: P
authors.lastname: Hamar
authors.forename: Balazs
authors.initials: B
authors.lastname: Antus
authors.forename: Laszlo
authors.initials: L
authors.lastname: Rosivall
authors.forename: Akos
authors.initials: A
authors.lastname: Koller
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D009392:Nephrectomy; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D006632:Histamine; D000241:Adenosine; D009638:Norepinephrine