1. The nitric oxide (NO) donor S-nitro-N-acetyl-penicillamine (SNAP) inhibits Helix aspersa heart activity and relaxes muscles. 2. K-free saline and ouabain both depress SNAP-induced relaxation in most experiments, but in a few preparations they either had no effect or potentiated SNAP-induced relaxation. 3. Na-K pump reactivation following preincubation in K-free saline leads to the pronounced transient relaxation of heart muscle, the magnitude of which depends on the duration of preincubation. 4. 0.1 mM SNAP inhibited the ouabain sensitive part of 86Rb uptake, which reflects Na-K pump activity. This inhibition is potentiated by phospholipase C. 5. SNAP increased cGMP levels in the heart. 6. These results indicate that SNAP-induced relaxation depends on Na and Ca gradients across the membrane, which suggests that Na:Ca exchange is involved in the mechanisms of SNAP-induced relaxation. It is postulated that SNAP elicits its inhibitory effect on the heart through a cGMP-dependent Na:Ca exchange.
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http://dx.doi.org/10.1016/s0306-3623(97)00302-9 | DOI Listing |
Am J Physiol Lung Cell Mol Physiol
January 2014
The Hospital for Sick Children Toronto, 555 Univ. Ave., Toronto, Ontario M5G 1X8, Canada.
Inhaled nitric oxide (NO) and other cGMP- or cAMP-dependent pulmonary vasodilators are often used in combination for the treatment of the persistent pulmonary hypertension of the newborn syndrome. There is in vitro evidence to indicate that NO downregulate the pulmonary vascular response to cGMP-dependent agonists raising concern as to whether a synergistic effect is observed when employing a combined strategy in newborns. Hypothesizing that a synergistic effect is absent, we evaluated newborn and juvenile rat pulmonary arteries to determine the individual and combined vasodilatory effect of cGMP- and cAMP-dependent agonists.
View Article and Find Full Text PDFPLoS One
September 2012
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Objective: Erectile dysfunction (ED) is considered as an early sign of vascular disease due to its high prevalence in patients with cardiovascular risk factors. Endothelial and neural dysfunction involving nitric oxide (NO) are usually implicated in the pathophysiology of the diabetic ED, but the underlying mechanisms are unclear. The present study assessed the role of oxidative stress in the dysfunctional neural vasodilator responses of penile arteries in the obese Zucker rat (OZR), an experimental model of metabolic syndrome/prediabetes.
View Article and Find Full Text PDFEur J Pharmacol
August 2008
Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531, Japan.
The roles of nitric oxide (NO) and K(+) channels in sustained relaxation induced by electrical field stimulation (EFS) in the presence of atropine and guanethidine were studied in circular muscle strips of mouse gastric fundus. In the wild-type mouse, N(G)-nitro-l-arginine (l-nitroarginine), a nitric oxide synthase inhibitor, significantly inhibited the sustained relaxation in addition to the rapid relaxation. The sustained relaxation in pituitary adenylate cyclase-activating peptide (PACAP)-knockout mouse, which was smaller than that of the wild-type mouse, was also inhibited by l-nitroarginine.
View Article and Find Full Text PDFEur J Pharmacol
March 2006
Department of Pharmacology, University of Aarhus, University Park 240, DK-8000 Aarhus C, Denmark.
In human resistance arteries the role of intracellular calcium during receptor agonist and nitric oxide (NO)-mediated vasorelaxation is almost unknown. We examined changes in smooth muscle calcium concentration ([Ca2+]i) caused by acetylcholine and the NO donor S-nitroso-N-acetylpenicillamine (SNAP) in isolated human subcutaneous small arteries. In arteries constricted with 50 mM KCl, acetylcholine and SNAP induced relaxation without any change in [Ca2+]i, whereas in noradrenaline constricted vessels, both acetylcholine and to a lesser degree also SNAP-mediated relaxation were associated with a decrease in [Ca2+]i.
View Article and Find Full Text PDFJ Urol
March 2006
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid and Servicio de Urología, Hospital Universitario Ramón y Cajal, Madrid, Spain.
Purpose: We investigated the role of the vascular endothelium and the L-arginine/nitric oxide pathway in the vasorelaxant effect of the phosphodiesterase type 5 inhibitor sildenafil in penile resistance arteries.
Materials And Methods: Second or third order branches of the horse deep intracavernous penile artery were mounted in microvascular myographs. The vasodilator effects of sildenafil and the NO donor SNAP (S-nitrosoacetyl-D,L-penicillamine) were evaluated in the absence and presence of the endothelium and inhibitors of the NO/cGMP (cyclic guanosine 3',5'-monophosphate) pathway.
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