Contractile hyporesponsiveness to norepinephrine of forearm veins in chronic renal failure.
BACKGROUND
We recently reported that endothelium-dependent relaxation is impaired in forearm veins from patients with chronic renal failure. However, assessment of responses to norepinephrine remains controversial. We examined the contractile response to norepinephrine in forearm veins from patients on chronic hemodialysis and the role of nitric oxide (NO), prostanoids, and Ca(2+)-activated K(+) channels in this response.


METHODS
Isometric contraction curves were obtained in rings of forearm vein from 21 dialyzed patients and 12 multiorgan donors in response to norepinephrine (1 nmol/L to 10 micromol/L) or KCl (5 to 100 mmol/L).


RESULTS
Veins from uremic patients were markedly less responsive to norepinephrine (7.6 +/- 0.6 g) and KCl (6.0 +/- 0.3 g) than those from organ donors (12.0 +/- 0.7 g and 10.4 +/- 0.5 g, respectively, P < .05). Treatment with N(G)-monomethyl-l-arginine (100 micromol/L), an inhibitor of NO synthase, or indomethacin (10 micromol/L), an inhibitor of prostacyclin synthesis, increased the response to norepinephrine in veins from control subjects but not in veins from dialyzed patients. Additional blockade of Ca(2+)-activated K(+) channels did not correct the hyporesponsiveness. In veins incubated in Ca(2+)-free solution containing either 100 mmol/L KCl or 1 micromol/L norepinephrine, addition of calcium chloride (0.1 to 30 mmol/L) elicited contractile responses that were significantly lower in veins from dialyzed patients.


CONCLUSIONS
The results demonstrate that norepinephrine-mediated contractions of forearm veins are markedly decreased in dialyzed patients. Endothelium-derived relaxing factors are not involved in this effect. The reduced contractile response is most likely caused by a decreased calcium entry through voltage- and receptor-dependent calcium channels.
Segarra
Gloria
G
Research Unit, Hospital Clinico Universitario, University of Valencia School of Medicine, Valencia, Spain.
Lluch
Paloma
P
Mauricio
Maria D
MD
Vila
José M
JM
Medina
Pascual
P
Martinez-León
Juan B
JB
Aldasoro
Martin
M
Lluch
Salvador
S
D004305:Dose-Response Relationship, Drug; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007676:Kidney Failure, Chronic; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects
D009638:Norepinephrine