Nitric Oxide-Mediated Vasodilatory Effect Of Atrial Natriuretic Peptide In Forearm Vessels Of Healthy Humans

Sakaguchi, Takashi; Ishibashi, Yutaka; Shimada, Toshio; Sakane, Takeshi; Takahashi, Nobuyuki; Ohata, Shuzo; Kodani, Nobuhiro; Kunizawa, Yoshitsugu; Inoue, Shinichi; Ohta, Y.; Nakamura, Ko; Shimizu, Hiromi; Katoh, Harumi; Murakami, Yo

doi:10.1046/j.1440-1681.2002.03597.x

Cited by 11 publications

(4 citation statements)

References 32 publications

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“…Our results can be contrasted with previous reports demonstrating that responses to ANP are attenuated by L ‐NMA, suggesting that, at least in part, ANP‐mediated relaxations are dependent on endothelial NO release (Brunner and Wolkart, 2001; Sugamori et al ., 2002). However, the idea that ANP releases NO to produce a vasodilator response remains controversial, given its well‐characterized action to directly generate cGMP.…”

Section: Discussioncontrasting

confidence: 99%

“…Firstly, functional antagonism produced by inhibition of eNOS will complicate the interpretation of studies that do not include a non‐NO‐dependent vasoconstrictor (Sugamori et al ., 2002). Secondly, we observed that sequential administration of ANP causes tachyphylaxis that could explain reduced ANP responses when using this experimental design (Brunner and Wolkart, 2001; Sugamori et al ., 2002). This observation is in line with the well‐characterized dephosphorylation and desensitization of NPR‐A (most likely by protein phosphatase 2A) (Potter and Garbers, 1992).…”

Section: Discussionmentioning

confidence: 99%

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Reciprocal regulation of human soluble and particulate guanylate cyclases in vivo

Madhani

Okorie

Hobbs

et al. 2006

British J Pharmacology

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Background & purpose: We demonstrated previously that reciprocal regulation of soluble (sGC) and particulate (pGC) guanylate cyclases by NO and natriuretic peptides coordinates cyclic cGMP-mediated vasodilatation in vitro. Herein, we investigated whether such an interaction contributes to vascular homeostasis in mice and humans in vivo. Experimental approach: Mean arterial blood pressure (MABP) changes in anaesthetized mice were monitored in response to i.v. administration of cGMP-and cAMP-dependent vasodilators in wild-type (WT), endothelial NO synthase (eNOS) and natriuretic peptide receptor (NPR)-A knockout mice. Forearm blood flow (FBF) in response to intra-brachial infusion of ANP (25, 50, 100, 200 pmol min -1 ) in the absence and presence of the NOS inhibitor N G -methyl-L-arginine (L-NMA; 4 mmol min -1 ) and the control constrictor noradrenaline (240 pmol min -1 ) was assessed in healthy volunteers. Key results: Sodium nitroprusside (SNP; NO-donor) and atrial natriuretic peptide (ANP) produced dose-dependent reductions in MABP in WT animals that were significantly enhanced in eNOS KO mice. In NPR-A K mice, SNP produced a dose-dependent reduction in MABP that was significantly greater than that in WT mice. Responsiveness to the cAMP-dependent vasodilator epoprostenol was similar in WT, eNOS KO and NPR-A KO animals. ANP caused vasodilatation of the forearm resistance vasculature that was significantly greater in individuals lacking endothelium-derived NO (i.e. L-NMA treated). Conclusions & implications:These data demonstrate that crosstalk occurs between the NO-sGC and ANP-pGC pathways to regulate cGMP-dependent vasodilatation in vivo in both mice and humans. These findings have implications for understanding the link between natriuretic peptide activity and cardiovascular risk.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reciprocal regulation of human soluble and particulate guanylate cyclases in vivo

Madhani

Okorie

Hobbs

et al. 2006

British J Pharmacology

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“…We demonstrated that the intra-arterial infusion of L-NMMA alone significantly attenuated changes in FBF during the infusions of ANP as previously shown by Sugamori et al (17), which seems to suggest an NO-dependent vasodilating effect of ANP. Costa et al also demonstrated an NO-dependent effect of ANP (18).…”

Section: Feasibility Of the No Clamp Techniquesupporting

confidence: 89%

Methodological Validity and Feasibility of the Nitric Oxide Clamp Technique for Nitric Oxide Research in Human Resistant Vessels

Ueda¹,

Wada²,

Umemura³

2004

Hypertens Res

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N(G)-methyl-L-arginine (L-NMMA) has been widely used for nitric oxide (NO) research, particularly for the assessment of NO-dependent vasodilatation evoked by agonists. However, such experiments may not be straightforward because L-NMMA causes vasoconstriction, which itself must non-specifically affect responses to any vasoactive agents. Therefore, in order to more accurately estimate the roles of NO in human vessels in vivo, we developed an NO clamp technique that uses co-infusion of an NO donor with L-NMMA. To assess the validity and feasibility of this technique, we compared the effects of intra-arterial infusion of L-NMMA on the forearm blood flow responses to vasodilators with and without the NO clamp technique in healthy males. All drugs were intra-arterially infused and changes in forearm blood flow (FBF) were measured by strain-gauge plethysmography. Vasodilatation evoked by atrial natriuretic peptide was significantly attenuated by L-NMMA alone (p = 0.001) but not by the NO clamp technique. L-NMMA significantly attenuated the responses to acetylcholine either with or without the NO clamp technique. However, the ratio of the area under the curve (AUC) of acetylcholine with L-NMMA to that without L-NMMA was significantly higher when the NO clamp technique was not used (AUC ratio: 0.62 +/- 0.13 vs. 0.48 +/- 0.14, respectively; p = 0.031). The contribution of NO to the FBF responses to vasodilators may be more properly assessed by the co-infusion of L-NMMA with the NO clamp technique than by L-NMMA alone. Our NO clamp technique thus appears to be valid and feasible for human NO research.

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“…Enzymatic disruption of the endothelium attenuated the ANP vasorelaxant effect on coronary circulation in a manner comparable to either blockade of nitric oxide synthase or inactivation of soluble guanylyl cyclase (sGC) [73]. Similar results were obtained in the human forearm under the effect of nitric oxide synthase blockade [74]. These findings suggested that NPs are potent endothelium-dependent agonists and that the relaxant action of ANP is in part mediated via endothelial receptors followed by activation of endothelial nitric oxide synthase and stimulation of smooth muscle sGC.…”

Section: Atrial Natriuretic Peptide and Nitric Oxide Systemsupporting

confidence: 57%

Atrial natriuretic peptide and regulation of vascular function in hypertension and heart failure

Rubattu¹,

Calvieri²,

Pagliaro³

et al. 2013

Journal of Hypertension

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Atrial natriuretic peptide (ANP) plays a pivotal role in modulation of vascular function and it is also involved in the pathophysiology of several cardiovascular diseases. We provide an updated overview of the current appraisal of ANP vascular effects in both animal models and humans. We describe the physiological implications of ANP vasomodulatory properties as well as the involvement of ANP, through its control of vascular function, in hypertension and heart failure. The principal molecular mechanisms underlying regulation of vascular tone, that is natriuretic peptide receptor type A/cyclic guanylate monophosphate, natriuretic peptide receptor type C, nitric oxide system, are discussed. We review the literature on therapeutic implications of ANP in hypertension and heart failure, examining the potential use of ANP analogues, neutral endopeptidase (NEP) inhibitors, ACE/NEP inhibitors, angiotensin receptor blocker (ARB)/NEP inhibitors, the new dual endothelin-converting enzyme (ECE)/NEP inhibitors and ANP-based gene therapy. The data discussed support the role of ANP in different pathological conditions through its vasomodulatory properties. They also indicate that ANP may represent an optimal therapeutic agent in cardiovascular diseases.

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Nitric Oxide-Mediated Vasodilatory Effect Of Atrial Natriuretic Peptide In Forearm Vessels Of Healthy Humans

Cited by 11 publications

References 32 publications

Reciprocal regulation of human soluble and particulate guanylate cyclases in vivo

Reciprocal regulation of human soluble and particulate guanylate cyclases in vivo

Methodological Validity and Feasibility of the Nitric Oxide Clamp Technique for Nitric Oxide Research in Human Resistant Vessels

Atrial natriuretic peptide and regulation of vascular function in hypertension and heart failure

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