Ca2+-activated K+ channels mediate relaxation of forearm veins in chronic renal failure

Martínez-León, Juan; Segarra, Gloria; Medina, Pascual; Vila, José M.; Lluch, Paloma; Peiró, Marta; Otero, Eduardo; Lluch, Salvador

doi:10.1097/00004872-200310000-00021

Cited by 21 publications

(29 citation statements)

References 45 publications

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“…Mullen et al (20) showed that the FMD response to hand warming is not attenuated by N-monomethyl-l-arginine, cyclooxygenase inhibition, or local autonomic nervous blockade. In patients who were on dialysis, vein relaxation was inhibited by tetraethylammonium chloride (inhibitor of Ca 2ϩ -activated K ϩ channels) but not N-monomethyll-arginine or asymmetrical dimethylarginine (43). In our study, serum 25(OH)D 3 and 1,25(OH) 2 D 3 levels were age-and SBP-independently and positively associated with FMD (Tables 2 and 3).…”

Section: Discussionsupporting

confidence: 44%

Mineral Metabolism and Arterial Functions in End-Stage Renal Disease

London¹,

Guérin²,

Verbeke

et al. 2007

Journal of the American Society of Nephrology

384

268

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, and the results of epidemiologic and clinical studies showed that large artery damage is a major factor that contributes to the mortality of these patients (2,3). The arterial system has two distinct, interrelated functions: To deliver an adequate blood supply from the heart to peripheral tissues (i.e., the conduit function) and to dampen blood flow and pressure oscillations that are caused by intermittent ventricular ejection (i.e., the cushioning function). Conduit function depends primarily on the diameter of the arterial lumen. It is highly efficient, and its physiologic adaptability is mediated through acute arterial diameter changes, which depend in large part on the endothelium response to alterations of shear stress, a phenomenon called flow-mediated dilation (FMD) (4). Conduit function disorders result from the narrowing of the arterial lumen or the diminished ability of the artery to dilate in response to shear stress changes. The cushioning function is altered by diminished distensibility that is caused by stiffening of arterial walls. Arterial stiffening results from fibroelastic intima thickening, increased collagen accumulation, and fragmentation of elastic lamellae with secondary fibrosis and calcification of the media (5).In patients with ESRD, both aspects of arterial functions are abnormal, characterized by arterial outward remodeling (6,7), increased arterial stiffening (6,7), and decreased FMD (8,9). These anomalies are enhanced further with aging, but these age-related effects are accelerated in uremic patients, in whom they are predictive of all-cause and cardiovascular mortality (3,10). The pathogenesis of these dysfunctions is not entirely clear. Conventional risk factors, such as aging and hypertension, only partly explain arterial abnormalities in patients with ESRD. Intimal and medial arterial calcifications (AC) are frequent in patients with ESRD (11); they result in arterial stiffening and abnormal conduit function and are associated with poor outcome (12). Several mineral metabolism disorders have been associated with increased AC and cardiovascular risk, including hyperphosphatemia, hyperparathyroidism, and increased calcium-phosphate product (13). Patients with chronic kidney disease and ESRD have vitamin D deficiency that is characterized by low serum 25-hydroxyvitamin D [25(OH)D 3 ] levels (14). With the decreased capacity of 1-␣-hydroxylase to synthesize calcitriol (1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]), the serum levels of the "hormonal" form of vitamin D also are low. Results of studies on the general population indicate that poor vitamin D status, characterized by low serum 25(OH)D 3 levels, is associated with higher prevalences of chronic heart failure, hypertension, and hyperparathyroidism (15-18), all fre-

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Section: Discussionsupporting

confidence: 44%

Mineral Metabolism and Arterial Functions in End-Stage Renal Disease

London¹,

Guérin²,

Verbeke

et al. 2007

Journal of the American Society of Nephrology

384

268

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“…Endothelial responsiveness was inhibited by calcium gated potassium channel blockade but not by inhibitors of NOS (ie, N G -monomethyl-L-aginine [L-NMMA] or ADMA). 19 Thus, substances other than inhibitors of NOS appear to be primarily responsible for the profound attenuation of EDV in ESRD patients.…”

mentioning

confidence: 99%

Letter to the Editor

Chan

Harvey

Böger

et al. 2005

ATVB

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“…Collectively, these results indicate that in MSVs, vasodilation induced by BK is mediated in part by prostacyclin and NO, and NO at intermediate and high TMPs, respectively. The dilator response to BK, which persisted in the presence of L -NNA and indomethacin, may be attributable to EDHF [19,22]. …”

Section: Discussionmentioning

confidence: 99%

“…The VSM BK Ca and endothelial cell SK Ca channels have been suggested to mediate endothelium-dependent vasodilation in several vascular preparations [19,22], but whether these ion channels are involved in BK-induced dilations of MSV has not previously been reported. To investigate the effects of BK Ca and SK Ca channels in mediating vasodilation responses to BK, MSVs were individually treated with paxilline and apamin, which significantly reduced the maximum dilation in response to BK by 41.9 ± 5.7 and 47.9 ± 2.8%, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…The inhibition of K Ca channels located in the VSM or endothelial cells of blood vessels would be considered a unique characteristic of the non-NO and nonprostanoid-type of vasodilation [16,17,18,19,21]. EDHF-induced relaxation in human large veins examined under isometric tension has been associated with activation of BK Ca channels [22], although vascular differences as well as species variation exist [23,24]. …”

Section: Introductionmentioning

confidence: 99%

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Effects of Acute Transmural Pressure Elevation on Endothelium-Dependent Vasodilation in Isolated Rat Mesenteric Veins

Enouri

Monteith²,

Johnson³

2013

J Vasc Res

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Background/Aims: The vascular regulatory function of the endothelium can be impaired by increases in transmural pressure (TMP). We tested the hypothesis that increasing TMP impairs the endothelial dilator function of rat mesenteric small veins (MSVs). Methods: In PGF2α-preconstricted MSVs, bradykinin (BK), sodium nitroprusside (SNP) and S-Nitroso-N-acetylpenicillamine (SNAP) concentration-response curves were generated at intermediate (6 mm Hg) and high (12 mm Hg) pressures. BK-induced vasodilation was examined in the absence and presence of nitric oxide synthase inhibitor [N^ω-nitro-L-arginine (L-NNA), 100 µM], cyclooxygenase inhibitor (indomethacin, 1 µM), and large (BK_Ca, paxilline, 500 nM) and small (SK_Ca, apamin, 300 nM) conductance Ca²⁺-activated K⁺ channel blockers. Results: BK, SNP and SNAP responses were not altered by TMP increases. BK-induced vasodilation was significantly reduced by L-NNA, indomethacin, apamin and paxilline at 6 mm Hg and L-NNA at 12 mm Hg, and was further reduced by coapplication of apamin and/or paxilline with L-NNA compared with responses obtained with either blocker. Endothelium removal completely abolished BK-induced vasodilation. Conclusion: Venous endothelial dilator function is not affected by TMP elevation. BK-induced vasodilation is completely dependent on the presence of functional endothelial cells and mediated in part by nitric oxide, BK_Ca and SK_Ca channels, while the participation of prostacyclin may be important at intermediate pressures.

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Ca2+-activated K+ channels mediate relaxation of forearm veins in chronic renal failure

Cited by 21 publications

References 45 publications

Mineral Metabolism and Arterial Functions in End-Stage Renal Disease

Mineral Metabolism and Arterial Functions in End-Stage Renal Disease

Letter to the Editor

Effects of Acute Transmural Pressure Elevation on Endothelium-Dependent Vasodilation in Isolated Rat Mesenteric Veins

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