Endothelium-Derived Vasoactive Substances in Bartter's Syndrome

Abstract

An imbalance between endothelium-derived vasoactive substances such as endothelin and endothelium-derived nitric oxide (NO) might be viewed as a possible determinant of vascular hyporeactivity. To check this possibility the authors evaluated the role of endothelin and NO in the reduced vascular reactivity of Bartter's syndrome. Plasma immunoreactive endothelin (22.07 +/- 7.06 vs 13.80 +/- 1.43 pmol/L, P < 0.011), urinary excretion of NO2- (0.28 +/- 0.10 vs 0.15 +/- 0.02, mumol/mumol of urinary creatinine, P < 0.01) and NO3- (0.17 +/- 0.07 vs 0.09 +/- 0.02 mumol/mumol of urinary creatinine, P < 0.011), and forearm resting blood flow (FRBF) (6.67 +/- 1.69 vs 4.30 +/- 0.38 mL/m'/100 mL, P < 0.005) were increased in patients with Bartter's syndrome in comparison with normal controls (C). No difference in postischemic maximal FBF was found (34.14 +/- 4.67 vs 31.35 +/- 2.86 mL/minute/100 mL), while patients showed a slower recovery after peak flow (PF) (77.57 +/- 61.35 vs 9.42 +/- 3.69 seconds, P < 0.013). Higher plasma endothelin supports the defect in vascular reactivity of Bartter's syndrome already shown for angiotensin II and norepinephrine and is in keeping with the altered intracellular calcium signaling previously demonstrated by the authors in this syndrome. The increased excretion of NO2- and NO3- in this syndrome, together with the higher FRBF and the slower recovery of the FBF and PF, argues in favor of an increased NO synthesis in Bartter's syndrome and of assigning it a role in the vascular hyporeactivity of Bartter's syndrome.

Forearm Nitric Oxide Balance, Vascular Relaxation, and Glucose Metabolism in NIDDM Patients

“…NO 2 " and NO 3 " assay. This assay was performed as previously described (28,29). Briefly, 5-ml blood samples were collected into tubes containing 1/5 isopropylic acid as preservative, and immediately centrifuged at 2,000 rpm.…”

Understanding the mechanisms of angiotensin II signaling involved in hypertension and its long-term sequelae

“…4). This Rho kinase downregulation in Bartter's and Gitelman's patients was associated with upregulation of nitric oxide system and increased nitric-oxide-mediated vasodilation, which is partly explained by increased expression of the endothelial subunit of nitric oxide synthase [16,44,45], compared with both hypertensive as well as healthy normotensive individuals [16,46,47]. These human findings parallel the upregulation of nitric oxide system upon Rho kinase inhibition found in vitro in endothelial cells and in vivo in Dahl hypertensive rats, and suggested to lead to cardiovascular protection [28,[48][49][50][51].…”

Angiotensin II and Cardiovascular-Renal Remodelling in Hypertension: Insights from a Human Model Opposite to Hypertension

“…release and PKC activation [7,23,24]. In addition, in these patients the evaluation of the NO system via the endothelial nitric oxide synthase mRNA levels, urinary excretion of NO metabolites and NO mediated vasodilation showed a significant increase of eNOS expression [25,26], an increased urinary excretion of NO metabolites, which positively correlated with urinary excretion of cyclic guanosine monophosphate (cGMP), the NO second messenger [25,27,28], and an increased NO mediated vasodilation compared with hypertensive patients [29] (Table 1). To these characteristics, which also underlie an antioxidant potential in these patients, it has to be added the demonstration of augmented expression of heme oxygenase 1 (HO-1) [30,31], known antioxidant and antiinflammatory enzyme.…”