Nitric oxide, prostanoid and non‐NO, non‐prostanoid involvement in acetylcholine relaxation of isolated human small arteries

Buus, Niels Henrik; Simonsen, Ulf; Pilegaard, Henriette; Mulvany, Michael J.

doi:10.1038/sj.bjp.0703041

Cited by 89 publications

(70 citation statements)

References 36 publications

(57 reference statements)

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“…11 The efficacy of this procedure was confirmed by abolition of relaxation to substance P and acetylcholine. Nitric oxide (NO) synthase was inhibited using NG-monomethyl-Larginine (L-NMMA), but, since L-NMMA has been reported to only partially inhibit release of NO in resistance arteries 12,13 we also used 1H- [ Table 1; Figure 2A), indicating no involvement of NO in this effect. The effect of CNP was inhibited by Rp-8-Br-cGMPS, an inhibitor of cGMP-dependent kinase (see Table 1; Figure 2B).…”

Section: Methodsmentioning

confidence: 99%

CNP, but not ANP or BNP, Relax Human Isolated Subcutaneous Resistance Arteries by an Action Involving Cyclic GMP and BKCa Channels

Garcha

Hughes

2006

J Renin Angiotensin Aldosterone Syst

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Natriuretic peptides play an important role in sodium regulation and blood pressure (BP) control. We examined the effects of atrial natriuetic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) on human isolated resistance arteries and the mechanisms involved in vasorelaxation. Human subcutaneous resistance arteries were mounted in an isometric myograph and contracted with phenylephrine. CNP, but not ANP or BNP, relaxed arteries in a concentration dependent manner. The action of CNP was unaffected by removal of the endothelium, inhibition of nitric oxide synthase by NG-monomethyl-Larginine or inhibition of soluble guanylate cyclase by 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Blockade of cyclic GMPdependent kinase by 8-bromoguanosine-3', 5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-Br-cGMPS) inhibited CNP relaxation. CNP relaxation was also inhibited by high potassium or iberiotoxin, indicating that it was due to opening of BK Ca channels. Omapatrilat, a vasopeptidase inhibitor of neutral endopeptidase and angiotensin-converting enzyme, enhanced the effect of CNP and inhibited responses to Ang I. In summary, CNP, but not ANP or BNP, relaxes human resistance arteries by activating cyclic GMP-dependent kinase and BK Ca . The effects of CNP are enhanced by vasopeptidase inhibition and this may contribute to the vasodilator effects of these agents in vivo.

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Section: Methodsmentioning

confidence: 99%

CNP, but not ANP or BNP, Relax Human Isolated Subcutaneous Resistance Arteries by an Action Involving Cyclic GMP and BKCa Channels

Garcha

Hughes

2006

J Renin Angiotensin Aldosterone Syst

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“…40,41 Other work suggests that cutaneous acetylcholine-mediated vasodilation may be relatively independent of NO or prostaglandins in humans. 42 …”

Section: Receptor-mediated Vasodilationmentioning

confidence: 99%

Decreased Microvascular Nitric Oxide–Dependent Vasodilation in Postural Tachycardia Syndrome

2005

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Background-One variant of postural tachycardia syndrome (POTS), designated low-flow POTS, is associated with decreased peripheral blood flow related to impaired local vascular regulation. Methods and Results-To investigate the hypothesis that microvascular endothelial dysfunction produces decreased peripheral blood flow in low-flow POTS, we performed experiments using laser-Doppler flowmetry (LDF) combined with iontophoresis in 15 low-flow POTS patients, 17 normal-flow POTS patients, and 13 healthy reference volunteers varying in age from 14 to 22 years. We tested whether ␣-adrenergic vasoregulation was impaired using iontophoretic delivery of tyramine, phentolamine, and bretylium followed by a norepinephrine dose response. We tested endothelial-dependent and -independent receptor-mediated vasodilation by measuring acetylcholine and sodium nitroprusside dose responses. We tested whether nitric oxide-dependent vasodilation was different in these groups by testing the local thermal hyperemic response to saline used as a reference compared with the nitric oxide synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME). Adrenergic and receptor-dependent cutaneous vasoregulation was similar for low-flow POTS, normal-flow POTS, and reference subjects. Thermal hyperemia produced distinctly different findings: there was marked attenuation of the nitric oxide-sensitive plateau during prolonged heating, which was insensitive to L-NAME in low-flow POTS subjects. The pattern of thermal hyperemia response in low-flow POTS subjects during saline administration resembled the pattern in reference subjects during L-NAME administration and was minimally affected by L-NAME. Conclusions-The

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“…Oxidative stress, a common phenotype in CF, reduces the bioavailability of NO in the arterioles (8,30), leading to subsequent development of microvascular dysfunction (48,56).…”

Section: Microvascular Function In Patients With Cfmentioning

confidence: 99%

Evidence of microvascular dysfunction in patients with cystic fibrosis

Rodriguez‐Miguelez

Thomas

Seigler

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Rodriguez-Miguelez P, Thomas J, Seigler N, Crandall R, McKie KT, Forseen C, Harris RA. Evidence of microvascular dysfunction in patients with cystic fibrosis. Am J Physiol Heart Circ Physiol 310: H1479 -H1485, 2016. First published April 15, 2016 doi:10.1152/ajpheart.00136.2016.-Cystic fibrosis (CF) is a genetic, multisystemic disorder with broad clinical manifestations apart from the well-characterized pulmonary dysfunction. Recent findings have described impairment in conduit vessel function in patients with CF; however, whether microvascular function is affected in this population has yet to be elucidated. Using laser-Doppler imaging, we evaluated microvascular function through postocclusive reactive hyperemia (PORH), local thermal hyperemia (LTH), and iontophoresis with acetylcholine (ACh). PORH [518 Ϯ 174% (CF) and 801 Ϯ 125% (control), P ϭ 0.039], LTH [1,338 Ϯ 436% (CF) and 1,574 Ϯ 620% (control), P ϭ 0.045], and iontophoresis with ACh [416 Ϯ 140% (CF) and 617 Ϯ 143% (control), P ϭ 0.032] were significantly lower in patients with CF than control subjects. In addition, the ratio of PORH to LTH was significantly (P ϭ 0.043) lower in patients with CF (55.3 Ϯ 5.1%) than control subjects (68.8 Ϯ 3.1%). Significant positive correlations between LTH and forced expiratory volume in 1 s (%predicted) (r ϭ 0.441, P ϭ 0.013) and between the PORH-to-LTH ratio and exercise capacity (r ϭ 0.350, P ϭ 0.049) were observed. These data provide evidence of microvascular dysfunction in patients with CF compared with control subjects. In addition, our data demonstrate a complex relationship between microvascular function and classical markers of disease severity (i.e., pulmonary function and exercise capacity) in CF. CYSTIC FIBROSIS (CF) is an inherited disorder that is predominantly characterized by pulmonary dysfunction; however, broader clinical manifestations, such as gastrointestinal, immune, endocrine, and musculoskeletal dysfunctions, are also present (36). Recently, our group reported conduit vascular endothelial dysfunction in young patients with CF (39). Importantly, this vascular impairment was observed in a population that exhibited preserved spirometric function and exercise capacity, which suggests a systemic consequence prior to the decrease in pulmonary function. Despite these recent observations, there appears to be a lack of understanding of the general functionality of the endothelium in CF.Impairments in endothelial function are highly related to a reduction in the bioavailability of nitric oxide (NO), a key vasodilator involved in the regulation of vessel tone and endothelium integrity (24). Decreases in NO balance have also been shown to contribute to impaired endothelial microvascular vasodilation (44). With use of laser-Doppler imaging technology, cutaneous blood flux can be quantified (45) to represent an accessible model of microvascular function (17). Postocclusive reactive hyperemia (PORH), local thermal hyperemia (LTH), and iontophoresis with acetylcholine (ACh), in combination with laser technology...

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Nitric oxide, prostanoid and non‐NO, non‐prostanoid involvement in acetylcholine relaxation of isolated human small arteries

Cited by 89 publications

References 36 publications

CNP, but not ANP or BNP, Relax Human Isolated Subcutaneous Resistance Arteries by an Action Involving Cyclic GMP and BKCa Channels

CNP, but not ANP or BNP, Relax Human Isolated Subcutaneous Resistance Arteries by an Action Involving Cyclic GMP and BKCa Channels

Decreased Microvascular Nitric Oxide–Dependent Vasodilation in Postural Tachycardia Syndrome

Evidence of microvascular dysfunction in patients with cystic fibrosis

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