TO THE EDITOR:
Yokokawa and colleagues [1] provide interesting data suggesting that increased nitric oxide production may contribute to the development of hemodialysis-induced hypotension. The authors speculate that individual patient sensitivity to heparin, an agent shown to promote nitric oxide production in cultured human vascular endothelial cells [2], may explain the increased production of nitric oxide seen in hypotensive patients, despite the administration of equal amounts of heparin. The mechanism by which increased nitric oxide production occurs, however, remains largely unknown.
Another complication of uremia—disordered hemostasis—is also thought to be related in part to platelet dysfunction associated with elevated nitric oxide levels [3, 4]. Interestingly, correction of anemia through transfusion or erythropoietin potentiates platelet function and improves the bleeding tendency associated with uremia. The effect of increased hematocrit to correct the uremic bleeding disorder may be related to the ability of the heme moiety to interfere with the release or production of nitric oxide [5]. A similar effect of increased hematocrit may blunt the nitric oxide-associated hypotension in patients receiving dialysis. Thus, it would be interesting to know whether a lower hematocrit or iron deficiency was present in the hypotensive group that had increased nitric oxide levels compared with the normotensive group.
1. Yokokawa K, Mankus R, Saklayen MG, Kohno M, Yasunari K, Minami M, et al. Increased nitric oxide production in patients with hypotension during hemodialysis. Ann Intern Med. 1995; 123:35-7.
2. Yokokawa K, Tahara H, Kohno M, Mandal AK, Yanagiasawa M, Takeda T. Heparin regulates endothelin production through endothelium-derived nitric oxide in human endothelial cells. J Clin Invest. 1993; 92:2080-5.
3. Remuzzi G, Perico N, Zoja C, Corna D, Macconi D, Vigano G. Role of endothelium-derived nitric oxide in the bleeding tendency of uremia. J Clin Invest. 1990; 86:1768-71.
4. Noris M, Benigni A, Boccardo P, Aiello S, Gaspari F, Todeschini M, et al. Enhanced nitric oxide synthesis in uremia: implications for platelet dysfunction and dialysis hypotension. Kidney Int. 1993; 44:445-50.
5. Luscher TF, Bock HA, Yang Z, Diederich D. Endothelium-derived relaxing and contracting factors: perspectives in nephrology. Kidney Int. 1991; 39:575-90.
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