Contractile Hyporesponsiveness to Norepinephrine of Forearm Veins in Chronic Renal Failure

• Published in: American journal of hypertension 2006-08, Vol.19 (8), p.818-822
• Main Authors: Segarra, Gloria, Lluch, Paloma, Mauricio, Maria D., Vila, José M., Medina, Pascual, Martinez-León, Juan B., Aldasoro, Martin, Lluch, Salvador
• Format: Article
• Language: English
• Subjects: Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Dose-Response Relationship, Drug; Female; Forearm - blood supply; Fundamental and applied biological sciences. Psychology; Human veins; Humans; Kidney Failure, Chronic; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; nitric oxide; norepinephrine; Norepinephrine - pharmacology; potassium channels; renal disease; Renal failure; Veins - drug effects; Vertebrates: urinary system
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2006.01.007

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. 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 μmol/L) or KCl (5 to 100 mmol/L). 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 μmol/L), an inhibitor of NO synthase, or indomethacin (10 μmol/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 μmol/L norepinephrine, addition of calcium chloride (0.1 to 30 mmol/L) elicited contractile responses that were significantly lower in veins from dialyzed patients. 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.