Increased endothelial nitric oxide synthase mRNA level in Bartter's and Gitelman's syndrome. Relationship to vascular reactivity.
OBJECTIVE
Patients with Bartter's syndrome and Gitelman's syndrome have reduced vascular reactivity, normo-hypotension and decreased peripheral resistances in spite of biochemical and hormonal abnormalities typical of hypertension. Since we found that both types of patients have increased urinary NO2-/NO3-, metabolites of NO, that correlated with their increased urinary cGMP, second messenger of NO, we examined the possible role of NO system in the pathophysiology of these syndromes.


METHODS
We used a molecular biologic approach and studied ecNOS gene expression by PCR-amplification of cDNA obtained by RT-PCR of RNA extracted by patients and healthy controls monocytes.


RESULTS
ecNOS is overexpressed in monocytes from patients with Bartter's and Gitelman's syndrome relative to controls: - 0.306 +/- 0.012 Densitometric Units (0.313 +/- 0.006, N = 3 for Bartter's patients; 0.302 +/- 0.009, N = 5 for Gitelman's patients) vs. 0.192 +/- 0.018, p < 0.0001.


CONCLUSIONS
This overexperession presumably accounts for their increased NO production; thus it could be likely that elevated ecNOS and NO levels are a part of pathophysiological process(es) that leads to their characteristic reduced vascular responses. However, the relationship between the alterations in the NO signalling system observed in this study and the mutations in either Na+-K+-2Cl cotransporter or in a K+ channel ROMK or in Cl- channel ClCNKB in Bartter's syndrome and in Na+-Cl- cotranstransporter in Gitelman's syndrome, recently reported as their primary defects remains to be defined.
Calò
L
L
Institute of Internal Medicine, Division of Nephrology, University of Padova, Italy.
Davis
P A
PA
Milani
M
M
Cantaro
S
S
Antonello
A
A
Favaro
S
S
D'Angelo
A
A
D000328:Adult; D001477:Bartter Syndrome / Q000378:metabolism*; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014655:Vascular Resistance