Chronic renal failure leads to reduced flow-dependent dilation in isolated rat skeletal muscle arterioles due to lack of NO mediation.
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.
Bagi
Zsolt
Z
Department of Pathophysiology, Semmelweis University, Budapest, Hungary. kolako@net.sote.hu
Hamar
Peter
P
Antus
Balazs
B
Rosivall
Laszlo
L
Koller
Akos
A
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
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D006632:Histamine; D000241:Adenosine; D009638:Norepinephrine