Role of K+Channels in Augmented Relaxations to Sodium Nitroprusside Induced by Mexiletine in Rat Aortas

2000 ◽  
Vol 92 (3) ◽  
pp. 813-820 ◽  
Author(s):  
Hiroyuki Kinoshita ◽  
Toshizo Ishikawa ◽  
Yoshio Hatano
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Guanylate Cyclase ◽  
Nitric Oxide Donor ◽  
Nitric Oxide Donors ◽  
K Channels ◽  
Vasodilator Effect ◽  
Isolated Rat

Background A class Ib antiarrhythmic drug, mexiletine, augments relaxations produced by adenosine triphosphate (ATP) sensitive K+ channel openers in isolated rat aortas, suggesting that it produces changes in the vasodilation mediated by ATP-sensitive K+ channels. Nitric oxide can induce its vasodilator effect via K+ channels, including ATP-sensitive K+ channels, in smooth muscle cells. Effects of mexiletine on arterial relaxations to nitric oxide donors, have not been studied. Therefore, the current study in isolated rat aortas was designed to (1) evaluate whether mexiletine augments relaxation in response to nitric oxide donors, including sodium nitroprusside, and (2) determine the role of K+ channels in mediating effects of mexiletine on such nitric oxide-mediated relaxation. Methods Rings of rat aortas without endothelia were suspended for isometric force recording. Concentration-response curves of sodium nitroprusside (10(-10) to 10(-5) M) and 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7; 10(-9) to 10(-5) M) were obtained in the absence and in the presence of mexiletine, in combination with a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo [4,3,-a]quinoxaline-1-one (ODQ), or inhibitors for ATP-sensitive K+ channels (glibenclamide), inward rectifier K+ channels (BaCl2), delayed rectifier K+ channels (4-aminopyridine), large conductance Ca2+-dependent K+ channels (iberiotoxin), or small conductance Ca2+-dependent K+ channels (apamin). Results Mexiletine (10(-5) or 3 x 10(-5) M) augmented relaxations to sodium nitroprusside and NOC-7. In arteries treated with glibenclamide (10(-5) M), mexiletine (3 x 10(-5) M) did not affect relaxations to nitric oxide donors, whereas mexiletine augmented relaxations to sodium nitroprusside despite the presence of BaCl2 (10(-5) M), 4-aminopyridine (10(-3) M), iberiotoxin (5 x 10(-8) M) and apamin (5 x 10(-8) M). Relaxations to sodium nitroprusside were abolished by ODQ (5 x 10(-6) M), whereas these relaxations were augmented by mexiletine (3 x 10(-5) M) in arteries treated with ODQ (5 x 10(-6) M). Conclusions These results suggest that ATP-sensitive K+ channels in vascular smooth muscle, contribute to the augmented vasodilator effect of a nitric oxide donor, sodium nitroprusside induced by mexiletine, and that the vasodilator effect is produced, at least in part, via the guanylate cyclase-independent mechanism.

Role of the nitric oxide donor sodium nitroprusside in the antidepressant effect of ketamine in mice

2015 ◽  
Vol 25 (10) ◽  
pp. 1848-1852 ◽  
Author(s):  
Miriam A. Vogt ◽  
Anne S. Vogel ◽  
Natascha Pfeiffer ◽  
Peter Gass ◽  
Dragos Inta
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Nitric Oxide Donor ◽  
Antidepressant Effect

The role of cGMP in the relaxation to nitric oxide donors in airway smooth muscle

1998 ◽  
Vol 341 (2-3) ◽  
pp. 225-233 ◽  
Author(s):  
Karen Stuart-Smith ◽  
David O. Warner ◽  
Keith A. Jones
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Nitric Oxide Donors

scholarly journals Constitutive LH receptor activity impairs NO-mediated penile smooth muscle relaxation

Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. 31-41
Author(s):  
Deepak S Hiremath ◽  
Fernanda B M Priviero ◽  
R Clinton Webb ◽  
CheMyong Ko ◽  
Prema Narayan
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Erectile Dysfunction ◽  
Sodium Nitroprusside ◽  
Signaling Pathway ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Activating Mutations

Timely activation of the luteinizing hormone receptor (LHCGR) is critical for fertility. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP) due to premature synthesis of testosterone. A mouse model of FMPP (KiLHRD582G), expressing a constitutively activating mutation in LHCGR, was previously developed in our laboratory. KiLHRD582G mice became progressively infertile due to sexual dysfunction and exhibited smooth muscle loss and chondrocyte accumulation in the penis. In this study, we tested the hypothesis that KiLHRD582G mice had erectile dysfunction due to impaired smooth muscle function. Apomorphine-induced erection studies determined that KiLHRD582G mice had erectile dysfunction. Penile smooth muscle and endothelial function were assessed using penile cavernosal strips. Penile endothelial cell content was not changed in KiLHRD582G mice. The maximal relaxation response to acetylcholine and the nitric oxide donor, sodium nitroprusside, was significantly reduced in KiLHRD582G mice indicating an impairment in the nitric oxide (NO)-mediated signaling. Cyclic GMP (cGMP) levels were significantly reduced in KiLHRD582G mice in response to acetylcholine, sodium nitroprusside and the soluble guanylate cyclase stimulator, BAY 41-2272. Expression of NOS1, NOS3 and PKRG1 were unchanged. The Rho-kinase signaling pathway for smooth muscle contraction was not altered. Together, these data indicate that KiLHRD582G mice have erectile dysfunction due to impaired NO-mediated activation of soluble guanylate cyclase resulting in decreased levels of cGMP and penile smooth muscle relaxation. These studies in the KiLHRD582G mice demonstrate that activating mutations in the mouse LHCGR cause erectile dysfunction due to impairment of the NO-mediated signaling pathway in the penile smooth muscle.

Relaxant effect of oxime derivatives in isolated rat aorta: role of nitric oxide (NO) formation in smooth muscle

2004 ◽  
Vol 67 (6) ◽  
pp. 1203-1214 ◽  
Author(s):  
Karel Chalupsky ◽  
Irina Lobysheva ◽  
Françoise Nepveu ◽  
Irina Gadea ◽  
Petra Beranova ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Rat Aorta ◽  
Relaxant Effect ◽  
No Formation ◽  
Oxime Derivatives ◽  
Isolated Rat

A new nitrosyl ruthenium complex nitric oxide donor presents higher efficacy than sodium nitroprusside on relaxation of airway smooth muscle

2011 ◽  
Vol 43 (5) ◽  
pp. 370-377 ◽  
Author(s):  
Patrícia F.S. Castro ◽  
Amanda de C. Pereira ◽  
Gerson J. Rogrigues ◽  
Aline C. Batista ◽  
Roberto S. da Silva ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Airway Smooth Muscle ◽  
Ruthenium Complex ◽  
Nitric Oxide Donor

Ketamine Stereoselectively Affects Vasorelaxation Mediated by ATP-sensitive K+Channels in the Rat Aorta

2002 ◽  
Vol 97 (4) ◽  
pp. 882-886 ◽  
Author(s):  
Mayuko Dojo ◽  
Hiroyuki Kinoshita ◽  
Hiroshi Iranami ◽  
Katsutoshi Nakahata ◽  
Yoshiki Kimoto ◽  
...  
Keyword(s):  
Sodium Nitroprusside ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Nitric Oxide Donor ◽  
K Channel ◽  
K Channels ◽  
Channel Opener ◽  
K Channel Opener ◽  
Isolated Rat

Background The effect of ketamine on vasodilation mediated by adenosine triphosphate (ATP)-sensitive K(+) channels has not been studied. The present study was designed to determine whether ketamine might stereoselectively affect vasorelaxation induced by an ATP-sensitive K(+) channel opener in the isolated rat aorta. Methods Rings of the rat aorta with or without endothelium were suspended for isometric force recording. During contraction to phenylephrine (3 x 10(-7) M), vasorelaxation in response to an ATP-sensitive K(+) channel opener levcromakalim (10(-8) to 10(-5) M) or a nitric oxide donor sodium nitroprusside (10(-10) to 10(-5) M) was obtained. Glibenclamide (10(-5) M), S(+) ketamine (10(-4) M), or ketamine racemate (10(-5) to 10(-4) M) was applied 15 min before addition of phenylephrine. Results Vasorelaxation induced by levcromakalim was completely abolished by an ATP-sensitive K(+) channel antagonist glibenclamide (10(-5) M) in the aorta with or without endothelium. Ketamine racemate (3 x 10(-5) to 10(-4) M) significantly inhibited this vasorelaxation in a concentration-dependent fashion, whereas S(+) ketamine did not affect the relaxation. However, the highest concentration of ketamine racemate and S(+) ketamine used in the present study did not alter vasorelaxation in response to sodium nitroprusside in the aorta without endothelium. Conclusion In the isolated rat aorta, clinically relevant concentrations of ketamine racemate can inhibit relaxation induced by an ATP-sensitive K(+) channel opener, whereas S(+) ketamine did not produce any inhibitory effect on this vasorelaxation. These results suggest that ketamine stereoselectively alters vasodilation ATP-sensitive K(+) channels in the conduit artery.

The role of nitric oxide in the regulation of the electrical activity of the trigeminal nerve in the rat

2021 ◽  
Author(s):  
S.O. Svitko ◽  
K.S. Koroleva ◽  
G.F. Sitdikova ◽  
K.A. Petrova
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Trigeminal Nerve ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
The Body ◽  
No Donor ◽  
No Signaling

Nitric oxide (NO) is a gaseous signaling molecule that regulates a number of physiological functions, including its role in the formation of migraine has been established. NO is endogenously produced in the body from L-arginine by NO synthase. The NO donor, nitroglycerin, is a trigger of migraine in humans and is widely used in the modeling of this disease in animals, which suggests the involvement of components of the NO signaling cascade in the pathogenesis of migraine. Based on the results obtained, it was found that an increase in the concentration of both the substrate for the synthesis of NO, L-arginine, and the NO donor, sodium nitroprusside, has a pro-nociceptive effect in the afferents of the trigeminal nerve. In this case, the effect of sodium nitroprusside is associated with the activation of intracellular soluble guanylate cyclase. Key words: nitric oxide, migraine, trigeminal nerve, L-arginine, guanylate cyclase, sodium nitroprusside, nociception.

Role of myocardium and endothelium in coronary vascular smooth muscle responses to hypoxia

2002 ◽  
Vol 282 (4) ◽  
pp. H1296-H1303 ◽  
Author(s):  
Cornel J. M. Kerkhof ◽  
Peter J. W. Van Der Linden ◽  
Pieter Sipkema
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Cardiac Tissue ◽  
Isometric Force ◽  
Adenosine Antagonist ◽  
Whole Heart ◽  
Muscle Responses ◽  
Isolated Rat

Hypoxia triggers a mechanism that induces vasodilation in the whole heart but not necessarily in isolated coronary arteries. We therefore studied the role of cardiomyocytes (CM), smooth muscle cells (SMC), and endothelial cells (EC) in coronary responses to hypoxia (Po 2 of 5–10 mmHg). In an attempt to determine the factor(s) released in response to hypoxia, we inhibited the contribution of adenosine, ATP-sensitive K+ channels, prostaglandins, and nitric oxide. Isolated rat septal artery segments without (−T) and with a layer of cardiac tissue (+T) were mounted in a double wire myograph, and constriction was induced. Hypoxia induced a decrease in isometric force of 21% and 61% in −T and +T segments, respectively ( P < 0.05). EC removal increased the relaxation to hypoxia in −T segments to 33% but had the same effect in +T segments (61%). Only one of the inhibitors, the adenosine antagonist in +T segments, partially affected the relaxation due to hypoxia. The role of adenosine is thus limited and other mechanisms have to contribute. We conclude that hypoxia induces a relaxation of SMC that is augmented by the presence of CM and blunted by the endothelium. A single mediator does not induce those effects.

Sign in / Sign up

Export Citation Format

Share Document